Genetics of the dentofacial variation in human malocclusion.

Malocclusions affect individuals worldwide, resulting in compromised function and esthetics. Understanding the etiological factors contributing to the variation in dentofacial morphology associated with malocclusions is the key to develop novel treatment approaches. Advances in dentofacial phenotyping, which is the comprehensive characterization of hard and soft tissue variation in the craniofacial complex, together with the acquisition of large-scale genomic data have started to unravel genetic mechanisms underlying facial variation. Knowledge on the genetics of human malocclusion is limited even though results attained thus far are encouraging, with promising opportunities for future research. This review summarizes the most common dentofacial variations associated with malocclusions and reviews the current knowledge of the roles of genes in the development of malocclusions. Lastly, this review will describe ways to advance malocclusion research, following examples from the expanding fields of phenomics and genomic medicine, which aim to better patient outcomes.

An MRI scale for assessment of haemophilic arthropathy from the International Prophylaxis Study Group.

Evaluation of prophylactic treatment of haemophilia requires sensitive methods. To design and test a new magnetic resonance imaging (MRI) scale for haemophilic arthropathy, two scales of a combined MRI scoring scheme were merged into a single scale which includes soft tissue and osteochondral subscores. Sixty-one joint MRI's of 46 patients with haemophilia were evaluated by four radiologists using the new and older scales. Forty-six of the joints were evaluated using two X-ray scales. For all MRI scores, interreader agreement and correlations with X-ray scores and lifetime number of haemarthroses were analysed. The interreader agreement intraclass correlation coefficient was 0.82, 0.89 and 0.88 for the soft tissue and osteochondral subscores and the total score, as evaluated according to the new MRI scale, compared to 0.80 and 0.89 as for the older scales. The total score and osteochondral subscore according to the new scale, as well as scores according to the older scales were correlated (P < 0.01) with number of haemarthroses (Spearman correlation 0.35-0.68) and with the X-ray scores (Spearman correlation 0.40-0.76), but no correlation (P > 0.05) was found between the soft tissue subscore of the new MRI scale and the X-ray scores. The new MRI scale is simpler to apply than the older and has similar reader reliability and correlation with lifetime number of haemarthroses, and by separating soft tissue and osteochondral changes it gives additional information. The new scale is useful for analyses of early and moderate stages of arthropathy, and may help to evaluate prophylactic haemophilia treatment.

Shiga-like toxin-converting phages from Escherichia coli strains that cause hemorrhagic colitis or infantile diarrhea.

Escherichia coli K-12 acquired the ability to produce a high titer of Shiga-like toxin after lysogenization by either of two different bacteriophages isolated from a highly toxinogenic Escherichia coli O157:H7 strain that causes hemorrhagic colitis. One of these phages and another Shiga-like toxin-converting phage from an Escherichia coli O26 isolate associated with infantile diarrhea were closely related in terms of morphology, virion polypeptides, DNA restriction fragments, lysogenic immunity, and heat stability, although a difference in host range was noted. These phages are currently the best-characterized representatives from a broader family of Shiga-like toxin-converting phages.

Cloning of Shiga-like toxin structural genes from a toxin converting phage of Escherichia coli.

The genes controlling high-level production of Shiga-like toxin (SLT) in Escherichia coli were cloned from the SLT converting phage 933J. This phage was isolated from a strain of E. coli that caused a foodborne outbreak of hemorrhagic colitis. The genes that convert normal E. coli to organisms producing high levels of toxin were cloned into the plasmid pBR328 and expressed in E. coli HB101. DNA restriction mapping, subcloning, examination of the cloned gene products by minicell analysis, neutralization, and immunoprecipitation with antibodies to SLT were used to localize the toxin converting genes and identify them as structural genes for SLT. Southern hybridization studies established that the DNA fragment carrying the cloned toxin structural genes had homology with the DNA of Shigella.

Candidate Gene Analyses of Skeletal Variation in Malocclusion.

This study evaluated associations between craniofacial candidate genes and skeletal variation in patients with malocclusion. Lateral cephalometric radiographs of 269 untreated adults with skeletal classes I, II, and III malocclusion were digitized with 14 landmarks. Two-dimensional coordinates were analyzed using Procrustes fit and principal component (PC) analysis to generate continuous malocclusion phenotypes. Skeletal class classifications (I, II, or III) were used as a categorical phenotype. Individuals were genotyped for 198 single-nucleotide polymorphisms (SNPs) in 71 craniofacial genes and loci. Phenotype-genotype associations were tested via multivariate linear regression for continuous phenotypes and multinomial logistic regression for skeletal malocclusion class. PC analysis resulted in 4 principal components (PCs) explaining 69% of the total skeletal facial variation. PC1 explained 32.7% of the variation and depicted vertical discrepancies ranging from skeletal deep to open bites. PC1 was associated with a SNP near PAX5 (P = 0.01). PC2 explained 21.7% and captured horizontal maxillomandibular discrepancies. PC2 was associated with SNPs upstream of SNAI3 (P = 0.0002) and MYO1H (P = 0.006). PC3 explained 8.2% and captured variation in ramus height, body length, and anterior cranial base orientation. PC3 was associated with TWIST1 (P = 0.000076). Finally, PC4 explained 6.6% and detected variation in condylar inclination as well as symphysis projection. PC4 was associated with PAX7 (P = 0.007). Furthermore, skeletal class II risk increased relative to class I with the minor alleles of SNPs in FGFR2 (odds ratio [OR] = 2.1, P = 0.004) and declined with SNPs in EDN1 (OR = 0.5, P = 0.007). Conversely, skeletal class III risk increased versus class I with SNPs in FGFR2 (OR 2.2, P = 0.005) and COL1A1 (OR = 2.1, P = 0.008) and declined with SNPs in TBX5 (OR = 0.5, P = 0.014). PAX5, SNAI3, MYO1H, TWIST1, and PAX7 are associated with craniofacial skeletal variation among patients with malocclusion, while FGFR2, EDN1, TBX5, and COL1A1 are associated with type of skeletal malocclusion.

Cat-scratch disease: report of a case with liver lesions and no lymphadenopathy.

The usual presentation of cat-scratch disease (CSD) is a subacute regional lymphadenitis following cutaneous inoculation. We present the case of a 10-yr-old white female with a 4-wk history of abdominal pain and fever, without associated lymphadenopathy. A 67Ga scintigram showed inhomogenous uptake by the liver. An abdominal computed tomographic (CT) scan revealed multiple low density lesions in the liver and the spleen, that were confirmed at laparotomy. Stellate microabscesses were seen on a wedge biopsy of the liver and a CSD antigen skin test was positive. CSD should be considered in the differential diagnosis of liver lesions, even in the absence of lymphadenopathy. This case emphasizes the importance of inhomogeneous 67Ga uptake by the liver.

Coverage of full-thickness burns with bilayered skin equivalents: a preliminary clinical trial.

A total of six patients have received bilayered skin-equivalent coverage of full-thickness burns, with takes of 50% to 70% in the later patients. These skin-equivalent grafts are constructed by combining allogeneic fibroblasts with collagen to form a sheet and adding a suspension of autologous epidermal cells to the surface of the collagen matrix. These bilayered skin-equivalent grafts have provided an expansion of at least fifteenfold to twentyfold for the area covered by the donor epidermis. By 8 months after grafting, the skin-equivalent grafts appeared smooth and approximated the color of normal skin. Long-term problems associated with hypertrophic scarring or graft fragility have not developed during the 18-month period of follow-up.

Review of gunshot wounds in Dayton, Ohio. Demographics, anatomic areas, results, and costs.

A retrospective review of 210 admissions for gunshot wounds was performed to evaluate the frequency that various anatomic areas were injured, complication rates, results of treatment, and costs. Seventy-two percent of patients had a single anatomic site involved. The complication rate was 13% and the death rate was 10.9%. A good result was obtained in 72%, but 12.4% had long-term disabilities. The average length of stay was 11 days with an average cost of +5,682 per patient. Application of today's prospective payment under diagnosis-related groups suggests this system of payment may adversely affect the delivery of trauma care in this country.

A correlation of response time and results of abdominal gunshot wounds.

Gunshot wounds to the abdomen are an indication for exploratory laparotomy in all cases except those involving the most superficial abdominal wall injuries. The charts of 123 patients admitted for abdominal gunshot wounds were reviewed for times of arrival on the scene by paramedics, in the emergency room, and in the operating room, as well as for number of admissions. Results of therapy were also graded and correlated with response times. The mean paramedic response time was 4 minutes 30 s. An average of 24 minutes 24 s was spent at the scene and in transport. The average delay from admission to arrival in the operating room was 1 hour 49 minutes. Patients who died spent an average of 54.4 minutes in the emergency room prior to surgical intervention. These results may represent justification for regionalization of trauma and direct transport to the operating room for abdominal gunshot wounds.

Primary hyperparathyroidism in a paediatric hospital.

We retrospectively reviewed the presentation and management of children with primary hyperparathyroidism (PHPT) from 1973 to 1995 at a paediatric tertiary-care centre. There were 11 patients (6 females), aged 12.3-17.7 years at presentation, with sporadic PHPT confirmed by histopathology (single adenoma). Presentation consisted of renal colic, or non-specific gastrointestinal, musculoskeletal or neurological symptoms. Misdiagnosis was common until hypercalcaemia was identified, 0.5-24 months after onset of symptoms (mean 7.7 months). All patients had hypercalcaemia and low-normal serum phosphate. The parathyroid hormone (PTH) radioimmunoassay used before 1986 was elevated in 1/4 patients; the intact PTH assay used after 1986 was elevated in 7/7 patients. At presentation, six had end-organ damage: band keratopathy, renal lesions, and/or bone disease. Preoperative localization was accurate in 0/4 patients diagnosed before 1986, but 5/7 patients diagnosed after 1986: three by ultrasound or sestamibi scan alone, and two by ultrasound and technetium scan. Surgical outcome was not dependent upon the accuracy of pre-operative localization. PHPT is rare in children but usually associated with end-organ damage, presumably due to delayed diagnosis. It should be considered in the differential diagnosis of unexplained non-specific complaints. The intact PTH assay greatly assists pre-operative diagnosis. The usefulness of pre-operative localization requires further research.

Repair of a subvalvular left ventricular aneurysm following mitral valve replacement.

Left ventricular aneurysms are a frequent complication of myocardial infarction. Some aneurysms occur secondary to trauma, previous operation, or infection. This report presents the case of a patient with a posterior submitral left ventricular aneurysm, which occurred following mitral valve replacement. The complete obliteration of the pericardial sac due to previous cardiac operation and the posterior location made external dissection of the aneurysmal wall technically impossible. Closure of the defect through the valve orifice by placing a patch over the neck of the aneurysm was found to be a relatively simple and safe technique combined with replacement of the prosthetic valve. The possibility of injury to the circumflex coronary artery was reduced using this surgical approach.

Composite resident work week.

During a 4-week period, all residents in the Wright State University School of Medicine Department of Surgery residency program were required to keep a log of their daily activities. Times were collected for the following resident activities: patient rounds, work-ups, laboratory data review, consults, meetings with attending physicians or patient families, phone calls, teaching conferences, medical student teaching, library time, clinics, attendance at codes, emergency department visits, on-call time, medical records committee meetings, and time scrubbed. The composite average weekly hours by resident year were 83.4 hours [postgraduate year (PGY)-1], 78.4 hours (PGY-2), 60.2 hours (PGY-3), 79.6 hours (PGY-4), and 80.9 hours (PGY-5). More than 50% of the resident work week cards were for less than 80 hours. Three activities (patient rounds, time scrubbed, and on-call) accounted for the majority of the residents' hours, but the average week, deleting educational and administrative hours, was less than 80 hours for all residents.

Surgical aspects of the Tenckhoff peritoneal dialysis catheter. A 7 year experience.

The experience with CAPD using the Tenckhoff catheter in 115 patients over a 7 year period has been reviewed. The general indications for CAPD in the patient with chronic renal failure are the mental and physical ability of the patient or his relatives to perform CAPD. In our series, diabetes mellitus has been a relative indication for CAPD, because diabetic patients often have vascular disease severe enough to make long-term hemodialysis difficult. The general contraindications are abdominal problems such as hernias, abdominal wall infections, inflammatory bowel disease, adhesions, and gastrointestinal stomas. Other contraindications are lumbar disk disease and respiratory insufficiency. The surgical principles of catheter insertion have been described. Complications associated with the Tenckhoff catheter were either mechanical (intraabdominal organ injury, incisional hernia, catheter leakage, catheter occlusion, or catheter dislodgement), or infectious (peritonitis or abdominal wall infection). The single most common organism isolated from effluent dialysate in 65 patients with peritonitis was Staphylococcus epidermidis in six patients (9.2 percent), and in 20 patients (30.8 percent), no organism could be isolated. For those patients who had peritonitis, the average frequency was at 8.9 months of CAPD. There were only three deaths (3 percent) directly related to the Tenckhoff catheter and these were due to peritonitis and sepsis. Only 22 (19 percent) of the 115 patients in this series had to discontinue CAPD because of its ineffectiveness or the patient's or relative's inability to perform CAPD.

Nutritional indicators of postburn bacteremic sepsis.

The potential of nutritional assessment parameters in predicting sepsis in burn patients was investigated. Sixty-two consecutive patients (mean age 41 years) with an average burn size of 19% were studied. Values were obtained on postburn day 10 for serum albumin, transferrin, nitrogen balance, total lymphocyte count, skin test reactivity, and percentage of ideal body weight. Parameters predictive of imminent septic episode included serum albumin less than 3.0 g/dl (p less than 0.001), total lymphocyte count less than 1500/mm3 (p less than 0.001), anergy (p less than 0.001), and serum transferrin less than 150 mg/dl (p less than 0.001). Nitrogen balance and percentage of ideal body weight were not found to contribute to group discrimination.

The use of phleborheography to detect deep venous obstruction.

Phleborheography is a noninvasive test to diagnose deep venous occlusion. Agreement with venography was 89 per cent in 147 examinations. Twenty-six hundred limbs were tested. Sixteen per cent (356 tests) demonstrated deep venous occlusion.

Immediate excision of burn wounds.

Early excision and grafting of body burns is a safe and efficient means of treatment. It reduces hospital stay and probably reduces septic complications. A group of 41 patients were so treated at Miami Valley Hospital Burn Therapy Program. Their hospital stay was less than that of patients treated and reported to the National Institute of Burn Medicine.

Elimination of urinary retention following inguinal herniorrhaphy.

In a group of 880 patients undergoing inguinal herniorrhaphy using local anesthesia, the incidence of postoperative urinary retention was 0.2 per cent. During the same period, a similar group of 200 patients had their hernias repaired using general or spinal anesthesia. The incidence of postoperative urinary retention was 13 per cent. The authors contend that the use of local anesthesia in inguinal hernia repair almost eliminates postoperative urinary retention.

Vascular complications as a result of intra-aortic balloon pumping.

Intra-aortic balloon conterpulsation (IABP) was used to assist 109 patients with extensive myocardial infarcts, unstable angina, cardiogenic shock, and unstable cardiodynamic states after cardiopulmonary bypass over a six year period. Severe vascular occlusion occurred in three patients (3%) which required an above the knee amputation. Each patient had a long history of smoking. Obesity, atherosclerotic disease of the femoral vessels, and extensive coronary artery disease were additional contributing factors. Two of the three patients survived, but both survivors had extensive postoperative myocardial infarctions. A low flow cardiac state and the presence of atherosclerotic changes in the legs must be precipitating factors for the vascular complications. Several possible methods to minimize complications of this nature include 1) angiographic examination of the lower aorta and femoral arteries at the time of cardiac catheterization, 2) frequent monitoring with ultrasound equipment, and 3) use of anticoagulation during and after the period of counterpulsation.

Acute appendicitis during pregnancy.

Forty-one appendectomies were performed on pregnant patients during the period 1973-1983. The preoperative diagnosis of acute appendicitis was correct in 57 per cent of the cases (24 patients). Presenting complaints, physical examinations, and laboratory analysis did not prove helpful in establishing the diagnosis. The incidence of acute appendicitis during pregnancy was 1:4172 (birth/pregnancy). Rapid surgical intervention probably contributed to the low (25%) incidence of perforated appendices. A transverse incision and general anesthesia were preferred. There was no maternal mortality and a 2 per cent rate of fetal loss.

Treatment of exposed bilateral Achilles tendons with use of the Dynasplint. A case report.

Third- and fourth-degree burns, which extend beyond the layers of the skin, are the most severe and difficult to rehabilitate. In this case report, a patient's recovery from exposed Achilles tendons bilaterally secondary to a severe burn injury is described. The Dynasplint, a spring-loaded orthosis designed to deliver a low-load, prolonged stretch to healing connective tissue, was used to facilitate the patient's recovery from an initial loss of -29 and -27 degrees of dorsiflexion of the right and left ankles, respectively. The patient's progress is reported from bed rest to independent ambulation at the time of discharge from the hospital.