30-Day Outcomes of Operative Versus Nonoperative Management for Humeral Diaphyseal Fractures in Patients with Concomitant Hip Fractures.

Every year over 330,000 people are hospitalized for hip fractures in the US. Of those patients, approximately 4-5% of patients with hip fractures present with a concomitant upper extremity fracture. Upper extremity (UE) fractures account for an estimated 2 million fractures a year. The number of hip fractures is projected to double by 2050. There is evidence that the presence of a concomitant upper extremity fracture results in an increased hospital length of stay (LOS), lower functional capacity upon discharge and higher mortality rates than seen with hip fractures in isolation. Additionally, hip fractures pose a significant economic burden and are expected to increase to over $62 billion in 2040. As such, hip fractures are a public health crisis. This study seeks to evaluate the differences in perioperative outcomes between nonoperative and operative management of humeral diaphyseal fractures in patients with concomitant hip fractures. (Journal of Surgical Orthopaedic Advances 29(2):99-102, 2020).

Evidence for a gene controlling the induction of transplantation tolerance.

Class I mismatched kidney transplantation in Massachusetts General Hospital MHC-defined miniature swine has been studied extensively as a model for induction of systemic allograft tolerance. In a large series of juvenile swine, long-term graft acceptance has been observed consistently following a 12-day course of cyclosporine. It was therefore surprising when three of five recipients in one of our studies rejected their grafts. Examination of the origins of the rejecting animals revealed that they were derived from a subline of the SLA(dd) miniature swine herd that was intentionally being inbred toward full homozygosity and had been inbred for eight generations prior to these experiments. A blinded study of additional class I mismatched renal transplants into animals from this subline confirmed the genetic basis of this rejection. We present here preliminary evidence suggesting that a likely explanation for this phenomenon is that the rejectors in this subline are homozygous for a recessive mutant allele of a gene normally involved in the induction of tolerance. Subsequent studies will be directed toward identification and characterization of the gene(s) involved, since existence of a similar genetic locus in humans might have implications for assessing an individual's likelihood of graft rejection versus tolerance induction prior to organ transplantation.

Twelve cases of exertional rhabdomyolysis in college football players from the same institution over a 23-year span: a descriptive study.

BACKGROUND: Rhabdomyolysis is a syndrome characterized by muscle necrosis that leads to release of the intracellular contents of muscle cells into the systemic circulation. Rhabdomyolysis due to overexertion is an uncommon but well-known severe complication of strenuous activity. Exertional rhabdomyolysis (ER) is typically described in weight lifters and military recruits undergoing basic training. Few cases have been reported in football players without known predisposing risk factors. We report our experience with this condition in college football players in a single institution. MATERIALS AND METHODS: College football players hospitalized for heat illness complicated by rhabdomyolysis were identified over a 23-year period. Clinical and laboratory findings were collected. Clinical course was recorded. RESULTS: Twelve patients were identified. All were Black males. One had sickle cell trait. BMI averaged 33 kg/m2 (range 23-45 kg/m2). Peak creatine phosphokinase (CPK) averaged 14,850 IU/L (range 1,021-109,616 IU/L). Serum creatinine averaged 1.9 mg/dl (range 1.2-3.1 mg/dl). Ten of twelve cases occurred in August. All responded to intravenous hydration with normalization of CPK and renal function. All returned to football. CONCLUSIONS: ER is a serious complication of strenuous physical activity that can threaten renal function. ER tends to occur in August, which coincides with the start of football practice when athletes are more likely to be detrained. The condition can occur in Black athletes in the absence of sickle cell trait. ER carries a good prognosis when recognized early and treated adequately.

Physicochemical and functional properties of Perinereis cultrifera (Grübe) erythrocruorin.

Perinereis erythrocruorin has the following physicochemical properties: So20,w = 55S, corresponding to a molecular weight around 2.7-10(6); minimum molecular weight (on the basis of the heme content) 23 700 +/- 500; isoelectric point 5.1; alpha-helix content approximately 40%. At alkaline pH values in the oxygenated form the 55-S molecules dissociate into subunits with a weight average sedimentation coefficient of 3S, corresponding to a molecular weight approximately 35 000. Deoxygenation of partially dissociated samples promotes association of the 3-S subunits into a 9S component. The functional properties of Perinereis erythrocruorin are characterized by a low cooperativity in oxygen binding (n 1/2 = 1.5) at neutral pH. Cooperativity increases reversibly towards both the acid and alkaline pH range, irrespective of changes in molecular weight. This finding, taken together with the ultracentrifuge results, suggests that a subunit may represent the functional unit of the protein. The pH dependence of the oxygen affinity can be accounted for in terms of a single oxygen linked group with a pK of 8.

Radioimmunoassay of regulatory peptides in the presence of acetonitrile: marked improvement of cholecystokinin assays.

Radioimmunoassay has made it possible to measure the levels of many hormones. However, samples for some hormones, such as cholecystokinin (CCK), need to be purified by reverse phase chromatography before assay. Usually, samples are eluted from cartridges or HPLC columns in about 50% acetonitrile, dried on a vacuum centrifuge, and then reconstituted in buffer. Drying and reconstituting samples is time consuming and introduces additional sources of error and peptide loss. The present study investigated the effect of acetonitrile on radioimmunoassays for CCK to see if samples containing acetonitrile could be assayed directly. The non-specific binding of a radiolabeled peptide, the zero binding (B0), and the fall in the presence of 2.5 fmol unlabeled CCK were determined in the presence of various proportions of acetonitrile with 0.1% TFA. Additionally, standard curves were compared in the presence and absence of 200microl of 50% acetonitrile, (n = 5). For assays using two separate CCK antisera, increasing amounts of acetonitrile gave progressively higher zero binding and fall, thereby increasing sensitivity and antibody titer. The use of 200microl 50% acetonitrile, chosen to represent typical sample conditions, increased antiserum titers by three to four-fold, as well as increasing sensitivity considerably. For one antiserum (CCK2), the IC20 was 0.36+/-0.02 fmol CCK/tube in the presence of acetonitrile and 1.45+/-0.08 fmol/tube in its absence (P< 0.001). For the other antiserum (Dino 7), the IC20 was 0.40+/-0.02 fmol CCK/tube in the presence of acetonitrile and 0.63+/-0.01 fmol/tube in its absence (P<0.001). A similar increase in sensitivity was seen with a gastrin assay. However, no significant change in the gastrin antibody titer was evident. Assays for several other hormones were unaffected by 200 microl of 50% acetonitrile. At volumes encountered in samples following chromatography, acetonitrile did not adversely affect radioimmunoassays for a number of hormones, and the sensitivity and antibody titer of the CCK assays were improved. Measurement of CCK samples without drying and reconstitution increases assay efficiency and sensitivity.

Esophageal manometry and 24-hour pH testing in the management of gastroesophageal reflux patients.

BACKGROUND: With rising interest in gastroesophageal reflux disease, an evaluation of the importance of manometry (M) and 24-hour pH testing (pH) for decisions regarding these patients is appropriate. METHODS: Two gastroenterologists and two surgeons were presented with history and physical examination, endoscopy, histology, and esophagram data ("DATA") from 100 patients and asked to make a treatment decision. After some time, either pH or M was added to DATA, and a further decision requested. Finally, DATA plus pH plus M was presented, and a decision was requested. Decisions were evaluated for changes in medical therapy, changes between medical and surgical therapy, and changes in type of surgery offered. RESULTS: Overall, 43% (173 of 400) of decisions were altered by the addition of both M and pH to DATA, with 28.5% (114 of 400) of decisions changed from medical therapy to surgery or vice versa by the addition of both tests to DATA. The addition of M alone changed decisions more often than pH alone especially with regard to the type of surgery offered (P <0.05). CONCLUSIONS: Together, M and pH alter clinical decisions and often alter the decision regarding surgery. Both tests appear important, but M more frequently alters overall management decisions and the type of surgery offered. Despite the need for cost containment, these clinical tools are essential to important decisions regarding the care of patients with gastroesophageal reflux disease.

Predictors of organ allograft tolerance following hematopoietic cell transplantation.

Using the miniature swine large animal model we have attempted to determine the relationship between tolerance and the presence of donor cells in the bone marrow, thymus and lineages of peripheral blood in a series of hematopoietic cell transplant recipients receiving delayed donor allografts without immunosuppression. Twenty-two animals receiving hematopoietic cell transplantation and a delayed organ allograft were analyzed. Assays for presence of donor CFUs in bone marrow (by PCR), thymic chimerism (by FACS and PCR/Southern Blot), peripheral blood chimerism (by FACS), and in vitro responsiveness to donor MHC were performed. Presence of donor BM CFUs, thymic chimerism and multilineage peripheral blood chimerism at the time of organ transplantation all correlated precisely with subsequent allograft tolerance (p < 0.001, p < 0.001, p < 0.005 respectively). These parameters were therefore accurate predictors (Positive Predictive Value (PPV) = 100% in all) of tolerance. In vitro assays of responsiveness were also highly associated (p < 0.002, p < 0.002 respectively), but were not as accurate predictors of subsequent organ tolerance (CML PPV = 80%). Engraftment, as indicated by the presence of donor derived CFU in the bone marrow, detectable thymic chimerism and multilineage peripheral blood chimerism are reliable predictors of subsequent donor allograft acceptance in hematopoietic cell transplant recipients.

Antibody-mediated activation of genetically defective Escherichia coli beta-galactosidases by monoclonal antibodies produced by somatic cell hybrids.

Six hybridomas producing monoclonal antibodies against Escherichia coli beta-galactosidase (beta-D-galactoside galoctohydrolase, EC 3.2.1.23) have been derived from two separate somatic cell fusions. Three of these antibodies can activate defective enzymes produced by strains of E. coli carrying Z-gene point mutations. In antigen excess, one monoclonal antibody shows similar enzyme binding and mutant-activating capacity. Characteristically, the former reaction has a 200-fold higher equilibrium constant. These data provide direct evidence that the enzyme-activation reaction is a single-hit event in which one antibody site favors the correct conformation of one active center of the enzyme. Because each "activating" hybridoma is able to activate several but not all point mutant enzymes tested, it appears that the correction of the genetic defect is produced by binding key sites of the protein three-dimensional structure rather than the sites affected by the mutation.

Effects of high-fat diet and cholecystokinin receptor blockade on promotion of pancreatic ductal cell tumors in the hamster.

The mechanism by which high-fat diets potentiate pancreatic cancer is not known, but pancreaticotrophic hormones such as cholecystokinin (CCK) may be involved. The effect of CCK receptor blockade on carcinogenesis during the entire promotion period was investigated in Syrian Golden hamsters fed a high- or low-fat diet and treated with N-nitrosobis(2-oxopropyl)amine (3 x 10 mg/kg at weekly intervals). One-half of the hamsters fed a high-fat diet received the CCK-A receptor antagonist devazepide (25 nmol/kg/hr) for the duration of the experiment. At 39 weeks the incidence of pancreatic malignancies was significantly higher in hamsters fed the high-fat diet than in those fed the low-fat diet (p < 0.05). Tumor incidence was not changed by CCK receptor blockade. Potentiation of pancreatic cancer by a high-fat diet in hamsters does not appear to be influenced by endogenous CCK during the tumor promotion period.

Laparoscopic antireflux surgery for the treatment of esophageal strictures refractory to medical therapy.

OBJECTIVE: The response of esophageal strictures to laparoscopic antireflux surgery remains controversial. The aim of this study was to examine the outcome of patients with medically refractory esophageal strictures caused by severe gastroesophageal reflux disease and treated surgically. METHODS: A prospective follow-up analysis was completed using data obtained from detailed specific questioning by an independent observer. Responses were rated for symptoms, dysphagia (range 1-19), satisfaction with treatment, well-being (1 = best, 10 = worst), and need for further therapy. RESULTS: Of 102 patients, 74 (72.5%) responded to follow-up. There were 31 women, mean age 59.6 yr, and 43 men, mean age 55.2 yr. Mean follow-up was 25 months (range 4-68 months). A total of 252 dilations before surgery decreased to 29 after surgery (p < 0.0001) in the mean observation period of 26 months before and 25 months after surgery (mean/patient 5.3 and 1.8, respectively, p < 0.001). The mean dysphagia score was 6.8 +/- 3.6 preoperatively and 3.7 +/- 1.4 postoperatively (p < 0.0001). Nine (12%) patients required continuous postoperative H2-blockers or proton pump inhibitors. Seven of these had gastritis or peptic ulcer disease. Before antireflux surgery, 10 (13.5%) had frequent pneumonia. No pneumonia was observed after surgery. Sixty-eight (91.9%) patients were satisfied with their decision to have surgery. Among these, the well-being score was 1.8 +/- 0.4 postoperatively vs 5.5 +/- 1.2 (p < 0.001) preoperatively. CONCLUSIONS: Laparoscopic surgery in patients with medically refractory esophageal strictures results in a good clinical outcome with minimal complications. Patients are very satisfied with relief of dysphagia, and there is a diminished need for further dilation, with good quality of life.