Analysis of MYO1H Gene Polymorphism in Skeletal Class-III Malocclusion Due to Mandibular Prognathism.

Background Mandibular prognathism (MP) is a craniofacial deformity resulting from the combined effects of environmental and genetic factors. Although various linkage and genome-wide association studies for mandibular prognathism have identified multiple strongly associated regions and genes, the causal genes and variants responsible for the deformity remained ambiguous. Aim This research work was aimed to study the association between polymorphism rs10850110 of the MYO1H gene and skeletal class-III malocclusion in our local population. Materials and Methods Thirty patients with skeletal class III due to mandibular prognathism in the study group and 30 patients with skeletal class I in the control group were selected for this study. These patients were from both sexes and above age 10 years. Based on the cephalometric values, patients were categorized into study and control groups. SNB (angle between sella, nasion and point B at nasion) greater than 82 degrees with an ANB (angle between point A, nasion and point B at nasion) of less than 0 degrees in the study group and ANB (angle between point A, nasion and point B at nasion) of 2 to 4 degrees in the control group were categorized. The polymorphism (rs10850110) of the MYO1H gene was genotyped using polymerase chain reaction and restriction fragment length polymorphism. Associations were tested with SNP exact test using SNPstats software. Results The single-nucleotide polymorphism rs10850110 showed a statistically significant association with mandibular prognathism. The G allele of marker rs10850110 (5' of myosin1H - MYO1H ) was overrepresented when compared with the "A" allele in mandibular prognathism cases ( p < 0.0001), and this was very significant. Conclusion These results suggest that the rs10850110 polymorphism of the MYO1H gene is associated with an increased risk for mandibular prognathism.

Differential regulation of threonine and tyrosine phosphorylations on protein kinase Cdelta by G-protein-mediated pathways in platelets.

Phosphorylation of activation loop threonine (Thr(505)) and regulatory domain tyrosine (Tyr(311)) residues are key regulators of PKC (protein kinase C) delta function in platelets. In the present study, we show that G(q) and G(12/13) pathways regulate the Thr(505) and Tyr(311) phosphorylation on PKCdelta in an interdependent manner. DiC8 (1,2-dioctanoylglycerol), a synthetic analogue of DAG (diacylglycerol), caused Thr(505), but not Tyr(311), phosphorylation on PKCdelta, whereas selective activation of G(12/13) pathways by the YFLLRNP peptide failed to cause phosphorylation of either residue. However, simultaneous activation by DiC8 and YFLLRNP resulted in Thr(505) and Tyr(311) phosphorylation on PKCdelta. In addition, we found that the activation of SFKs (Src family tyrosine kinases) is essential for G(12/13)-mediated Tyr(311) phosphorylation of PKCdelta. These results were confirmed using G(q)-deficient mouse platelets. Finally, we investigated whether Thr(505) phosphorylation is required for Tyr(311) phosphorylation. A T505A PKCdelta mutant failed to be phosphorylated at Tyr(311), even upon stimulation of both G(q) and G(12/13) pathways. We conclude that (i) PKCdelta binding to DAG, downstream of G(q) pathways, and its translocation results in Thr(505) phosphorylation, (ii) G(12/13) pathways activate SFKs required for the phosphorylation of Tyr(311) on Thr(505)-phosphorylated PKCdelta, and (iii) Thr(505) phosphorylation is a prerequisite for Tyr(311) phosphorylation on PKCdelta.

Pneumocystis carinii pneumonia after heart transplantation.

Five patients with Pneumocystis carinii pneumonia after heart transplantation are reported. Four had severe clinical symptoms, whereas 1 was asymptomatic. Mechanical ventilatory support was necessary in 1 because of respiratory distress. Pneumocystis carinii infection developed in 4 patients within the first 4 postoperative months, and 1 patient had clinical disease 1 year after transplantation with a recurrence 9 months later. All were treated with trimethoprim-sulfamethoxazole either orally or intravenously (10 to 20 mg.kg-1.day-1 of trimethoprim). All patients recovered from infection and received the same drug prophylactically for 2 to 20 months after the infection. All patients are doing well after Pneumocystis carinii infection except 1 who died after an acute myocardial infarction 4 years after infection. We conclude that trimethoprim-sulfamethoxazole is an effective agent for the treatment of Pneumocystis carinii pneumonia after heart transplantation.

Calcified thrombus in the right atrium: a rare complication of long-term parenteral nutrition in a child.

A 5-year-old boy with short-bowel syndrome who receives home parenteral nutrition developed a calcified thrombus that involved the inferior vena cava (IVC) and the right atrium. Symptoms included 3 to 4 months of intermittent fever and 2 months of vague chest pain. Blood could not be aspirated from the IVC catheter and an IVC contrast study demonstrated the calcified thrombus. The intracardiac portion of the mass was removed surgically, but the IVC mass could not be completely excised. The boy developed a pericardial effusion 6 weeks after surgery. He was treated for this and 6 months after the initial surgery the patient was asymptomatic.

A suggested technique for harvest of the cardiac graft from the heart-lung recipient in domino heart transplantation.

The performance of the domino heart transplant operation presents unusual technical problems related to preservation of the sinus node and integrity of the venae cavae. An alternative technique that may simplify this procedure is suggested.

Rabbit antithymocyte globulin. A 10-year experience in cardiac transplantation.

Rabbit antithymocyte globulin, a "custom-made" pan-anti-T-cell antibody produced in rabbits, is currently being evaluated in the United States and may, within several years, become approved by the Food and Drug Administration. Because we have used this agent for induction of immunosuppression for 10 years in cardiac recipients and because the results appear to be more favorable than those obtained with other agents (horse antithymocyte globulin, antilymphocyte globulin, OKT3), we have reviewed our experience. For the purpose of analysis, all non-bridge-to-transplant cardiac recipients have been divided into three groups on the basis of immunosuppression protocol: group I (March 1979 to January 1983), 28 patients treated with rabbit antithymocyte globulin, steroids, and azathioprine; group II (January 1983 to March 1985), 29 patients treated with rabbit antithymocyte globulin, cyclosporine, and steroids; and group III (March 1985 to January 1989), 98 patients treated with rabbit antithymocyte globulin, cyclosporine, steroids, and azathioprine. Actuarial data showed advantage for group III in survival rate (1 year 94%, 2 years 91%, 3 years 88%), freedom from rejection (30% free at 1 year), freedom from infection (50% free at 1 year), freedom from death from rejection (99% free at 1 year), and freedom from death from infection (97% freedom at 1 year). Actuarial survival rates and freedom from death from rejection and infection are comparable for any of our groups with contemporary published data. In the past 3 years, we have had no death from acute rejection or from posttransplant infection. Time-related rates of infection by etiologic agents have shown a significant reduction in early bacterial, viral, and nocardial infections between groups I and III. With rabbit antithymocyte globulin 200 mg intramuscularly every day for 3 days, our current protocol, T-cells are significantly reduced and local and systemic toxicity is almost unnoticeable. A progressively increasing cyclosporine dose along with rapid tapering steroid and maintenance azathioprine immunosuppressive induction appears to be the therapy of choice in cardiac transplantation.

Thromboembolic complications of the Symbion AVAD System.

The Symbion Acute Ventricular Assist Device (AVAD) System is an experimental paracorporeal pulsatile ventricular assist device (VAD) for single or biventricular assist. Eleven patients were implanted but 2 died within 24 h and were excluded from the study. Nine patients, four with left ventricular assist devices (LVADs) and five with biventricular assist devices (BIVADs), with a mean implant time of 24 days, were studied to determine the incidence and site of thrombus formation within the device and the incidence of thromboembolic complications. Anticoagulation consisted of heparin titrated to keep the partial thromboplastin time (PTT) twice control and dipyridamole 50 to 200 mg q6h p.o. Seven of nine patients (78%) developed thrombus; five had thrombus visible within the clear housing of the device during the implant period, and two patients had thrombus discovered only after VAD explantation. Common sites of formation were the diaphragm-housing junction, the housing near the outflow orifice, and the de-airing port. Three patients with thrombus developed thromboembolic complications; two suffered strokes and one had multiorgan emboli. The Symbion AVAD System has significant thrombogenic properties that may limit its clinical application.

Heart-lung transplantation: the initial Arizona experience.

Since November 1985, cardiopulmonary transplantation has been performed at the University of Arizona heart transplant program. Seven patients, five women and two men, have undergone heart-lung transplantation. Five patients had primary pulmonary hypertension, and two patients had Eisenmenger's complex. The mean age was 31 years (range, 17 to 43 years). Average follow-up was 15 months (range, 3 to 34 months), with a total of 115 patient-months. There have been no operative or late deaths. Immunosuppression consisted of rabbit antithymocyte globulin, cyclosporine (Cyclosporin A), azathioprine, methylprednisolone, and prednisone. Our first five patients were aggressively diagnosed and treated for rejection by endomyocardial biopsy, with each patient having one or several treatments for acute rejection. These five patients had one or several episodes of severe infection, particularly cytomegalovirus. In our last two patients we omitted routine heart biopsies. Only those rejection episodes diagnosed by chest x-ray films are considered significant. Our last two patients have not been treated for acute rejection and have had no infections. Presently our immunologic surveillance consists only of careful clinical examination and frequent chest x-ray films. Any changes in the patient's condition are aggressively investigated, searching for infection or rejection. Two patients have been used as domino donors of their native heart.

Extracorporeal pulsatile biventricular support after cardiac transplantation.

A donor heart failed to adequately sustain hemodynamic function after cardiac transplantation. The cause of the donor heart dysfunction was unknown, and there were no definite risk factors identified to suggest the heart would not recover. A Symbion Acute Ventricular Assist Device System was used to support both ventricles. The heart gradually recovered and the system was explanted after 1 week of support. The patient recuperated and has been discharged from the hospital.

Transtracheal aspiration and fine needle aspiration biopsy for the diagnosis of pulmonary infection in heart transplant patients.

A total of 129 transtracheal aspirations or fine needle aspirations, or both, were performed in 65 heart and heart-lung transplant patients to identify the causative pathogen in suspected pulmonary infection. Transtracheal aspiration was performed in 82 instances, fine needle aspiration in 47, and both procedures in 23. Both transtracheal and fine needle aspiration were highly specific, 96% and 100%, respectively. Sensitivity for transtracheal aspiration was lower than for fine needle aspiration, 70% and 89%, respectively. The lower sensitivity of transtracheal aspiration is attributed to its performance in all patients with suspected infection regardless of chest radiographic findings. Fine needle aspiration was performed when identifiable lesions could be used as a "target." Overall accuracy of transtracheal aspiration was 78% compared to 91% for fine needle aspiration both alone and combined with transtracheal aspiration. More invasive procedures such as bronchoalveolar lavage and open lung biopsy were required in only three patients (2%). Transtracheal aspiration resulted in one minor complication (1%). The commonest complication of fine needle aspiration was pneumothorax (21%). There were no deaths associated with either procedure. We conclude that in heart and heart-lung transplant patients with suspected pulmonary infection, transtracheal aspiration and fine needle aspiration are safe and accurate methods to identify the causative organism. More invasive techniques may be required in a small minority of patients.

Early experience with the total artificial heart as a bridge to cardiac transplantation.

There is no doubt that currently available biventricular pneumatic pulsatile devices placed orthotopically with transcutaneous drive lines can support life in patients who may then be successfully transplanted. For the most part, the world experience is with the Jarvik hearts. The current model of choice is the 70-cc device because it is smaller and may be implanted with less fear of "fit problems" than the 100-cc model. As Case 4 illustrates, a fit problem may cause a fatal outcome. But if special precautions in implantation are taken, these may be avoided (Case 6). The fears of excessive bleeding, hemolysis, embolism, and infection with the use of these devices are not as prohibitive as we suspected. Bleeding is always a threat in complex cardiac surgery with grafting. Hemolysis is not a problem if excessive transfusion can be avoided. Embolism and infection may be inevitable, but as our patient B.C. has proven, there is no need to rush immediately to transplantation. And if the implanted patient does not meet local transplant selection criteria, we have enough information now to recommend that they not be accepted for transplantation. Bleeding may be anticipated to be a major problem in any patient with dense reactive scar tissue. To avoid this, transplantation should be done within 3 weeks. We recommend patients who have previously been selected for orthotopic transplantation and begin an accelerated decompensation (our Cases 2 and 7) as the best candidates for temporary orthotopic mechanical support. In these patients, there is no question about whether recovery of the native heart is possible or whether a reversible myocardial insult is present. The plan to do an orthotopic transplant indicates that a cardiectomy is necessary. Case 5, who was in reasonable shape for transplantation, was also favorable. In cases of anticipated graft failure, early use of the Jarvik 7-70 is recommended. This type of device, when suitably placed, provides excellent control of the circulation. There is no requirement for intensive care of the native heart, since it is gone, along with toxic antiarrhythmic medications, risk of embolizing a mural thrombus, and the constant balancing of a univentricular device vis-á-vis the native heart. Further, if pulmonary edema is present with accompanying elevation in pulmonary vascular resistance, the biventricular device requires only an upward adjustment in right drive pressure. With a univentricular device one must worry not only about the pulmonary vascular resistance but also about the capacity of the right heart to pump at a normal output.(ABSTRACT TRUNCATED AT 400 WORDS)

Ventricular performance and myocardial water content during hemodilution in dogs.

In dogs anesthetized with chloralose-urethan on right heart bypass, left ventricular (LV) performance was assessed at constant LV stroke work before and for up to 2.5 h after crystalloid hemodilution was established. Lowering the hematocrit from 43.3 +/- 1.3% to 13.6 +/- 1.7% (SE) did not significantly change LV end-diastolic pressure (LVEDP) initially. After 80 min LVEDP increased slightly by 1.7 +/- 0.6 cmH2O (P less than 0.05) at a stroke work of 17.3 +/- 2.3 g.m. The value of dP/dt did not change significantly throughout. When LV function curves were generated by increasing cardiac output, the stroke work attained at an LVEDP of 10 cmH2O decreased with hemodilution from 23.9 +/- 3.5 to 20.8 +/- 3.9 g.m (NS). LV wall water content increased with hemodilution, from which it could be calculated that there was an 18.6% increase in LV mass. Thus, despite an increase in LV external girth demonstrated by LV circumferential gauges, it is possible that increased wall thickness due to the water gain resulted in little change or an actual decrease in LV end-diastolic volume. Thus, profound hemodilution can be attained with only slight depression of LV performance.

Acute pancreatitis: analysis of factors influencing survival.

Of patients with acute pancreatitis (AP), there remains a group who suffer life-threatening complications despite current modes of therapy. To identify factors which distinguish this group from the entire patient population, a retrospectiva analysis of 519 cases of AP occurring over a 5-year period was undertaken. Thirty-one per cent of these patients had a history of alcoholism and 47% had a history of biliary disease. The overall mortality was 12.9%. Of symptoms and signs recorded at the time of admission, hypotension, tachycardia, fever, abdominal mass, and abnormal examination of the lung fields correlated positively with increased mortality. Seven features of the initial laboratory examination correlated with increased mortality. Shock, massive colloid requirement, hypocalcemia, renal failure, and respiratory failure requiring endotracheal intubation were complications associated with the poorest prognosis. Among patients in this series with three or more of these clinical characteristics, maximal nonoperative treatment yielded a survival rate of 29%, compared to the 64% survival rate for a group of patients treated operatively with cholecystostomy, gastrostomy, feeding jejunostomy, and sump drainage of the lesser sac and retroperitoneum.