Effect Of Surgical Repair Research Articles

192. DYSPNOEA IMPROVES FOLLOWING PARAOESOPHAGEAL HERNIA REPAIR AND IS NOT NECESSARILY A CONTRAINDICATION TO SURGERY

Abstract Paraoesophageal hernias (PEH) are often symptomatic and can lead to life-threatening complications including volvulus and ischaemia. Dyspnoea was recently reported as the most prevalent symptom of giant PEHs, although it has been perceived by some as a contraindication to surgery. The aim of this study is to evaluate the effect of surgery on resolution of dyspnoea amongst patients with giant hiatus hernia defined as greater than 30% of the stomach above the diaphragm. Data were extracted from a prospectively maintained single-surgeon database containing records of patients undergoing composite hernia repair. Patients who underwent standardised composite laparoscopic repair of giant PEH without mesh prosthesis between March 2009 and December 2015 and had documented dyspnoea were included. Patients were reviewed post-operatively at 6 weeks, 3 months, 12 months, and then annually unless more frequent visits were clinically indicated. The primary outcome of the analysis was the difference in patient-reported pre-operative and post-operative dyspnoea. Secondary outcomes included differences in pre-operative and post-operative dysphagia and clinical aspiration as well as recurrence of PEH of any size. Inclusion criteria were met by 154 patients. There were 127 females (82.5%) and 27 males (17.5%). The average age at time of operation was 71.2 years (range 49–93, SD 9.66). The average hernia size was 64%, based on intraoperative evaluation by the surgeon (range 30–100%, SD 20.2). After surgery, there was a significant improvement in all symptoms: dyspnoea (100% pre-operatively, 2.6% post-operatively, P¬ < 0.001), dysphagia (46.1% pre-operatively, 15.6% post-operatively, P < 0.001) and clinical aspiration (9.1% pre-operatively, 1.3% post-operatively, P = 0.002). Hernia recurrence was found in 37 patients (24.0%) amongst whom dyspnoea was rare (5.4%, 2 patients). This study suggests that dyspnoea resolves following laparoscopic repair of giant paraoesophageal hernia. This may be explained by the effect of surgical repair on improving hernia-related atrial compression, pulmonary congestion and reduced lung capacities. The presence of dyspnoea should be regarded as an indication rather than a barrier to surgery. Therefore, we recommend all patients with giant hiatus hernia to be assessed by a specialist surgical service.

Long noncoding RNAs regulated spermatogenesis in varicocele-induced spermatogenic dysfunction.

ObjectivesTo evaluate the expression, potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the pathogenesis of varicocele (VC)‐induced spermatogenic dysfunction.Materials and MethodsWe established a rat model with left experimental VC and divided rats into the sham group, the VC group, and the surgical treatment group (each group, n = 10). Haematoxylin and eosin (HE) staining and sperm quality were analysed to evaluate spermatogenesis function. LncRNA expression profiles were analysed using lncRNA‐Seq (each group n = 3) and validated using quantitative real‐time polymerase chain reaction (each group n = 10). Correlation analysis and gene target miRNA prediction were used to construct competing endogenous RNA network. The regulated signalling pathway and spermatogenic dysfunction of differentially expressed lncRNAs (DE lncRNAs) were validated by Western blot.ResultsHE detection and sperm quality analysis showed that VC could induce spermatogenic dysfunction. Eight lncRNAs were upregulated and three lncRNAs were downregulated in the VC group compared with the sham group and surgical treatment group. The lncRNA of NONRATG002949.2, NONRATG001060.2, NONRATG013271.2, NONRATG022879.2, NONRATG023424.2, NONRATG005667.2 and NONRATG010686.2 were significantly negatively related to sperm quality, while NONRATG027523.1, NONRATG017183.2 and NONRATG023747.2 were positively related to sperm quality. The lncRNAs promote spermatogenic cell apoptosis and inhibit spermatogonia and spermatocyte proliferation and meiotic spermatocytes by regulating the PI3K–Akt signalling pathway.ConclusionDE lncRNAs may be potential biomarkers for predicting the risk of spermatogenic dysfunction in VC and the effect of surgical repair. These DE lncRNAs promote spermatogenic dysfunction by regulating the PI3K–Akt signalling pathway.

Effects of surgical repair of obstetric fistula on severity of depression and anxiety in Ethiopia

BackgroundThe surgical repair of fistula can address the physical symptoms, but may not end the psychological challenges that women with fistula face. There are a few studies that focus on women with this condition in Ethiopia. Hence, the aim of this study was to determine the effects of surgical repair of obstetric fistula on the severity of depression and anxiety in women with obstetric fistula in Ethiopia.MethodThe study employed a longitudinal study design to investigate the changes in 219 women with obstetric fistula admitted to six fistula management hospitals in Ethiopia. The data were collected on admission of the patients for obstetric fistula surgical repair and at the end of six-month post repair. A structured questionnaire was used to obtain socio-demographic information and medical history of the respondents. Depression and anxiety symptoms were measured using the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7) scales. The data was entered using Epi-Data software and then exported to SPSS for further analysis. The Mann-Whitney-U test, the Kruskal-Wallis test and Paired t-test were performed to measure the change in psychological symptoms after surgical repair.ResultThough 219 respondents were interviewed pre-obstetric fistula surgical repair, only 200 completed their follow up. On admission, the prevalence of depression and anxiety symptoms were 91 and 79% respectively. After surgical repair, the prevalence rate was 27 and 26%. The differences in the prevalence of screen-positive women were statistically significant (P < 0.001).ConclusionThe study concluded that the severity of depression and anxiety symptoms decrease post-obstetric fistula surgical repair. However, a woman with continued leaking after surgery seems to have higher psychological distress than those who are fully cured. Clinicians should manage women with obstetric fistula through targeted and integrated mental health interventions to address their mental health needs.

Subacromial space volume in patients with rotator cuff tear: The effect of surgical repair

ObjectiveThe aim of this study was to evaluate the effect of the rotator cuff tear repair on subacromial space volume. MethodsWe retrospectively identified 21 eligible patients (5 males and 16 females; mean age: 56.4 (range; 46–71) years) who had shoulder arthroscopy for unilateral full-thickness small to medium rotator cuff tear and normal controlateral shoulder joint. The mean follow-up time was 16.1 (range; 12–25) months. Preoperative and postoperative 1 year bilateral shoulder MRIs and Constant scores were reviewed. Subacromial volume was calculated by using Osirix software. Pre-, postoperative and healthy side (contralateral control group) subacromial volumes were recorded. Paired sample and t-tests were used to compare the pre- and postoperative groups. Independent sample t-tests were used to compare the healthy and pre- and postoperative groups. The correlation between the changes in the subacromial volume and the shoulder Constant score were analyzed using Pearson correlation analyses. ResultsThe mean subacromial volume of the preoperative group was 2.95 cm3 (range; 1.53–4.23) and the postoperative group was 3.59 cm3 (range; 2.12–4.84). The volume increase was statistically significant (p < 0.05). The mean subacromial volume of the control group was 3.93 cm3 (range; 2.77–5.03), and the difference between the preoperative group and the control group was statistically significant. There was no significant difference found between the postoperative group and the control group (p = 0.156). There was no significant correlation found between the volume and the constant score changes (r = 0.170, p = 0.515). ConclusionThe subacromial space volume significantly decreases in full-thickness rotator cuff tears smaller than 3 cm and the surgical repair increases the subacromial volume significantly. Level of evidenceLevel IV; Diagnostic Study.

Clinical Features of Patients with Post-Traumatic Canalicular Laceration and the Effectiveness of Surgical Repair with Monoka Tube Intubation

Clinical Features of Patients with Post-Traumatic Canalicular Laceration and the Effectiveness of Surgical Repair with Monoka Tube Intubation

Computationally Efficient Magnetic Resonance Imaging Based Surface Contact Modeling as a Tool to Evaluate Joint Injuries and Outcomes of Surgical Interventions Compared to Finite Element Modeling

Joint injuries and the resulting posttraumatic osteoarthritis (OA) are a significant problem. There is still a need for tools to evaluate joint injuries, their effect on joint mechanics, and the relationship between altered mechanics and OA. Better understanding of injuries and their relationship to OA may aid in the development or refinement of treatment methods. This may be partially achieved by monitoring changes in joint mechanics that are a direct consequence of injury. Techniques such as image-based finite element modeling can provide in vivo joint mechanics data but can also be laborious and computationally expensive. Alternate modeling techniques that can provide similar results in a computationally efficient manner are an attractive prospect. It is likely possible to estimate risk of OA due to injury from surface contact mechanics data alone. The objective of this study was to compare joint contact mechanics from image-based surface contact modeling (SCM) and finite element modeling (FEM) in normal, injured (scapholunate ligament tear), and surgically repaired radiocarpal joints. Since FEM is accepted as the gold standard to evaluate joint contact stresses, our assumption was that results obtained using this method would accurately represent the true value. Magnetic resonance images (MRI) of the normal, injured, and postoperative wrists of three subjects were acquired when relaxed and during functional grasp. Surface and volumetric models of the radiolunate and radioscaphoid articulations were constructed from the relaxed images for SCM and FEM analyses, respectively. Kinematic boundary conditions were acquired from image registration between the relaxed and grasp images. For the SCM technique, a linear contact relationship was used to estimate contact outcomes based on interactions of the rigid articular surfaces in contact. For FEM, a pressure-overclosure relationship was used to estimate outcomes based on deformable body contact interactions. The SCM technique was able to evaluate variations in contact outcomes arising from scapholunate ligament injury and also the effects of surgical repair, with similar accuracy to the FEM gold standard. At least 80% of contact forces, peak contact pressures, mean contact pressures and contact areas from SCM were within 10 N, 0.5 MPa, 0.2 MPa, and 15 mm2, respectively, of the results from FEM, regardless of the state of the wrist. Depending on the application, the MRI-based SCM technique has the potential to provide clinically relevant subject-specific results in a computationally efficient manner compared to FEM.

Effects of surgical repair on active shoulder position sense and 3-dimensional reaching accuracy in a patient with anterior shoulder instability

The purpose of this report was to investigate whether a subject with anterior shoulder instability exhibited better active shoulder position sense and 3-dimensional (3-D) reaching accuracy after a surgical repair. The 19-year-old male subject underwent an open Bankart repair procedure for his left shoulder followed by a standardized post-operative rehabilitation program. Shoulder position sense was examined with traditional passive matching and active positioning protocols. Reaching accuracy in space with the unrestricted arm motion was also examined. The subject was tested 5 months prior to the surgery and re-tested 6 months after the surgery. With the traditional passive matching protocol, shoulder position sense improved <2° after surgery. However, shoulder position sense improved greatly after surgery with active shoulder abduction (up to 4.25°) and active shoulder rotation (up to 5.87°) testing protocols. In addition, reaching accuracy also greatly improved after surgery (up to 10.97 cm) with the most significant improvement when reaching to targets located in the frontal plane. Data suggest that anterior shoulder repair with rehabilitation can improve both active shoulder position sense and reaching accuracy, especially in shoulder positions involving abduction with external rotation.

Effectiveness of surgical reconstruction to restore radiocarpal joint mechanics after scapholunate ligament injury: An in vivo modeling study

Disruption of the scapholunate ligament can cause a loss of normal scapholunate mechanics and eventually lead to osteoarthritis. Surgical reconstruction attempts to restore scapholunate relationship show improvement in functional outcomes, but postoperative effectiveness in restoring normal radiocarpal mechanics still remains a question. The objective of this study was to investigate the benefits of surgical repair by observing changes in contact mechanics on the cartilage surface before and after surgical treatment. Six patients with unilateral scapholunate dissociation were enrolled in the study, and displacement driven magnetic resonance image-based surface contact modeling was used to investigate normal, injured and postoperative radiocarpal mechanics. Model geometry was acquired from images of wrists taken in a relaxed position. Kinematics were acquired from image registration between the relaxed images, and images taken during functional loading. Results showed a trend for increase in radiocarpal contact parameters with injury. Peak and mean contact pressures significantly decreased after surgery in the radiolunate articulation and there were no significant differences between normal and postoperative wrists. Results indicated that surgical repair improves contact mechanics after injury and that contact mechanics can be surgically restored to be similar to normal. This study provides novel contact mechanics data on the effects of surgical repair after scapholunate ligament injury. With further work, it may be possible to more effectively differentiate between treatments and degenerative changes based on in vivo contact mechanics data.

Female genital mutilation/cutting and orgasm before and after surgical repair

Summary Introduction Female genital mutilation/cutting (FGM/C) is often performed to decrease women's sexual pleasure. Removal of the external clitoris may particularly impair pleasure and orgasmic functioning. Aims and methods This review evaluates the literature on: the orgasmic functioning of women with FGM/C whose clitorises have and have not been excised and; the effect of surgical repair on orgasm. A PubMed search was performed to identify all published studies of FGM/C that included an assessment of orgasm. Results While three of the seven FGM/C studies that included a control group found decreased orgasmic functioning in affected women, no study fully controlled for demographic differences between groups or separated the FGM/C group by clitoral integrity. The impact of FGM/C on orgasm therefore remains unknown; however, indirect evidence suggests that orgasm rates would be reduced in women who cannot engage in direct stimulation of the external clitoris. Surgical defibulation releases the infibulation scar and appears to improve global sexual functioning but not orgasm. Clitoral reconstructive surgery, which creates a new external clitoris, restores a more normal genital appearance, resolves pain at the excision site, and increases clitoral pleasure. One large study found that it enabled clitoral orgasm in approximately 40% of patients. Since rates of orgasm from all forms of stimulation (e.g., vaginal) were not assessed, it is unclear for how many women an external clitoris is necessary for orgasm. Conclusions Future studies on FGM/C and orgasm should address the methodological limitations of previous research. Although clitoral reconstruction allows many women with FGM/C to become clitorally orgasmic, it does not guarantee orgasm. Women should be offered psychotherapy to improve their sexual or orgasmic functioning regardless of their genital integrity.

Effect of surgical repair on testosterone production in infertile men with varicocele: A meta‐analysis

To determine the effect of surgical varicocele repair in improving testicular Leydig cell function as shown by increased testosterone production. Eligible studies were searched in Medline and the Pubmed database, and cross-referenced as of 31 May 2011 using the terms "varicocele,""testosterone" and "surgery." The database search, quality assessment and data extraction were independently carried out by two reviewers. Only studies including patients with testosterone evaluation before and after surgery were considered for the analysis. A systematic review and meta-analysis was carried out for continues variables using random effect models. Out of 125 studies, a total of nine were selected, including 814 patients. The combined analysis showed that mean serum testosterone levels after surgical treatment increased by 97.48 ng/dL (95% confidence interval 43.73-151.22, P=0.0004) compared with preoperative levels. Surgical treatment of varicocele significantly increases testosterone production and improves testicular Leydig cell function.

Blow-out fractures: Patterns of ocular motility and effect of surgical repair

The decision to repair an orbital blow-out fracture depends on several factors, but evidence for the optimum timing of surgery is not clear. We retrospectively studied all patients with orbital injuries who were referred to the eye department at a Scottish teaching hospital over a 10-year period from 1997 to 2006. We aimed to document the incidence and pattern of disturbances of ocular motility after blow-out fractures, and identify the rates of early and late resolution of these deficits, both spontaneously and after surgical repair. We found that most patients with blow-out fractures had a motility defect for an acute phase; approximately one third of which resolved spontaneously within 2 weeks. Recovery of motility after orbital surgery occurred in less than half the patients, and was not immediate. Continuing recovery also occurred in those who did not undergo surgery. Entrapment of muscle or tissue is not the only cause of motility disturbance after blow-out fractures, and orbital surgery is only one aspect of management in those patients with persistent motility defects.

Direction of Preoperative Ventricular Shunting Affects Ventricular Mechanics After Tetralogy of Fallot Repair

Tetralogy of Fallot (TOF) typically results in clinical cyanosis or volume overload of the left ventricle (LV), depending on the direction and magnitude of shunting across the ventricular septal defect (VSD). The present study examines the effects of surgical TOF repair on LV mechanics and compares these changes between patients with VSD shunts that are predominantly right-to-left (R-L; "blue TOF") and those with VSD shunts that are predominantly left-to-right (L-R; "pink TOF"). Eleven patients (6 R-L and 5 L-R) 4.3 to 18.4 months old (median 7.1 months old) were studied. LV end-diastolic area (EDA) was calculated from transesophageal echocardiograms obtained during initiation and weaning of cardiopulmonary bypass. LV end-diastolic pressure was measured by micromanometer. Compliance was assessed by end-diastolic pressure-area curves. Contractility was assessed from preload recruitable stroke work by the stroke work-versus-LV EDA relation. VSD shunt direction was determined by preoperative Doppler echocardiography. Changes in LV function at the conclusion of cardiopulmonary bypass included decreased stroke area (from 6.6 +/- 0.9 to 4.1 +/- 0.4 cm(2)/m(2), P=0.012) and ejection fraction (from 55 +/- 2% to 41 +/- 3%, P<0.001). LV EDA at a common pressure in 8 patients decreased (from 10.4 +/- 1.4 to 7.6 +/- 1.2 cm(2)/m(2), P=0.003), which suggests a decrease in ventricular compliance. Additionally, the end-diastolic pressure-area curves shifted to the left in all patients. Preload recruitable stroke work decreased (from 34.8 +/- 2.4 to 21.8 +/- 2.6 mm Hg, P=0.007), which demonstrates a decrease in ventricular contractility. When separated by preoperative shunt direction, LV EDA increased in R-L patients by 0.9+/-0.5 cm(2)/m(2) postoperatively but decreased in L-R patients by 4.3 +/- 0.8 cm(2)/m(2) (P<0.001). Area ejection fraction decreased in all patients independent of shunting or change in LV EDA. LV diastolic and systolic function are depressed after TOF repair. Mechanical effects of the VSD patch and myocardial depressant effects of ischemia and reperfusion during surgery probably contribute to the observed changes in LV mechanics. Different effects of surgical repair on LV preload in pink and blue TOF also contribute to the spectrum of clinical results observed after surgery.

The effects of surgical repair on P-wave dispersion in children with secundum atrial septal defect

Atrial septal defect (ASD) is one of the most common congenital heart diseases in children. P-wave dispersion has been reported to be associated with non-homogeneous propagation of sinus impulses. The heterogeneity of atrial conduction time may predispose the atria to arrhythmias. The aim of this study was to determine the impact of surgical repair on P-wave indices in children with isolated secundum ASD. Children with isolated secundum ASD undergoing surgical repair (n=50; mean age, 7.0+/-3.0 years) and healthy controls (n=51; mean age, 7.6+/-2.7 years) were compared. Maximum P-wave duration (Pmax), shortest duration (Pmin) and P-wave dispersion (Pd) were measured using 12-lead surface electrocardiography. Mean Pmax was found to be significantly higher in children with ASD compared with controls (95.2+/-10.8 vs 84.1+/-9.2 msec; P<0.001), and Pd before surgery was significantly higher compared with controls (47.4+/-12.0 vs 38.8+/-9.7 msec; P<0.001). Both P-wave indices were significantly decreased within the first year after surgical closure - the values decreased to those comparable to healthy controls (Pmax, 86.2+/-9.7 msec; Pd, 39.8+/-10.7 msec; P>0.05). Surgical closure of ASD in children decreases Pmax and P-wave conduction time. We speculate that earlier closure of the defect may play an important role in avoiding permanent changes in the atrial myocardium and atrial fibrillation in adulthood.

CFTR gene therapy, a method to rescue lung hypoplasia in congenital diaphragmatic hernia?

despite progress in neonatal care and despite changing concepts in treatment in the recent years, the mortality rate of infants with congenital diaphragmatic hernia (CDH) remains high ([20][1]). Pulmonary hypoplasia and vascular alterations associated with CDH have tremendous postnatal functional

Factores hemodinámicos y retraso de crecimiento en operados de comunicación interauricular

Ostium secundum-type atrial septal defect (ASD) is usually well tolerated, without severe complications in childhood. However, in many patients its effect on growth is disproproportionate when compared with that of more serious congenital heart disease. To test the hypothesis that hemodynamic disturbances are responsible for failure to thrive in congenital heart disease, we studied growth and the effect of surgical repair in children with ASD. The study was performed in 72 patients who underwent surgery at a mean age of 8 years and 8 months. The mean follow-up was 17 months. Somatometric and hemodynamic parameters were studied and the correlation between them was verified. The effect of surgery and of age at operation on somatometric changes was evaluated. Fifty-two percent of the patients were malnourished and height was affected in 28 %. The correlation between weight and age at operation was r 5 0.78 (p < 0.05) for the entire group, r 5 0.81 (p < 0.05) for the malnourished subgroup and r 5 0.88 (p < 0.05) for the subgroup with normal nutrition. No relationship was found between hemodynamic and somatometric parameters. Surgery improved growth disturbances but not in all patients (weight: from 52 % to 32 %; height: from 28 % to 16 %). Hemodynamic factors are not the only cause of growth and nutritional alterations.

Comparison of Surgically Attached and Non-Attached Repair of the Rat Achilles Tendon-Bone Interface. Cellular Organization and Type X Collagen Expression

The effects of surgical repair versus non-repair on cell morphology and type X collagen expression were investigated using a rat model of Achilles tendon avulsion. The animals were divided into four groups. In Group I, tendon was reattached to the original attachment site by suturing through a drill hole in the calcaneus; in Group II, tendon was not reattached and a drill hole was not made; in Group III, tendon was not reattached but a drill hole was made; and the animals in Group IV were sham operated.In Group I (tendon reattached), at 2 weeks postoperatively, many hypertrophic chondrocytes appeared at the reattachment site adjacent to bone and type X collagen was detected immunologically both in the cells and in the extracellular matrix. After 4 weeks, the cells at the original site of attachment were arranged in rows along the newly formed tendon fibers and were stained with type X collagen antibody. By contrast, when tendon was not reattached (Groups II and III), a gap between the original attachment site and the tendon stump was observed through the entire postoperative period. At 8 weeks, the original attachment site was covered by fibrocartilaginous tissue and tendon became attached to the calcaneal fibrocartilage area, which is proximal to the original attachment site. Type X collagen was detected in the cells which were adjacent to bone. In Group IV (sham operation), there were no changes in histology or type X collagen distribution, either at the attachment site or in tendon and bone, compared with the non-operated control rats. These results suggest that surgical reattachment of tendon to the original site is important to help reorganize cells during the repair process. Type X collagen was identified immunohistochemically in the cells adjacent to hone in all the groups, suggesting that it may play a role in maintaining distinct areas of calcified and non-calcified fibrocartilage.

Effect of surgical repair on the neurologic function in infants with lipomeningocele.

Eighteen children under the age of 1 year underwent surgery for lipomeningocele at our institution between 1983 and 1991. All the patients had neurologic exams and urodynamic studies (UDS) including a cystometrogram and electromyography of the external urethral sphincter pre- and postoperatively. The surgical procedure performed included an untethering of the spinal cord, laser debulking of the lipoma and placement of a dural graft. All the infants presented with a lesion on their back. Two of 10 infants with a normal neurological exam had abnormal UDS preoperatively. Early surgery normalized abnormal preoperative UDS in 5 of 6 (83%) infants with abnormal UDS. Moreover, 3 of 8 (38%) infants with an abnormal neurological exam preoperatively improved after surgery and none worsened. These observations suggest that abnormal urinary tract function in infants with lipomeningocele may be reversible with early prophylactic surgery.

Results of Surgical Repair Versus Splinting of E xperimentally Transected Muscle

Complete muscle tears or transections can be treated by splinting or surgical repair. Although repair is often advocated in the young and athletic population, no well-controlled studies compare the results of splinting and surgical repair. I studied the effects of surgical repair versus splinting only of transected muscles in an experimental model. In group I (n = 14), a unilateral transection of the extensor digitorum longus (EDL) muscle of the Sprague-Dawley rat was treated with splinting only. In group II (n = 14), the muscle was surgically repaired as well. Active and passive strength measurements at day 7 and 14 showed an earlier return of passive strength in group II at day 7. No statistically significant differences at day 14 were noted. In this model, earlier return of active and passive strength occurred in surgically repaired muscle disruption as compared with nonrepaired muscles.

Subcostal slide for diaphragmatic hernia repair

A technique of closing large congenital diaphragmatic hernial defects without significant tension is described. Suggested advantages are: the simplicity of the technique; minimising the adverse effects of surgical repair on lung compliance; maintenance of the dome shape of the diaphragm, thus sparing intra-abdominal volume; and improved cosmetic results in the long term.

Effects of surgical repair on respiratory mechanics in congenital diaphragmatic hernia: H. Sakai, M. Tamura, Y. Hosokawa, et al. J Pediatr 111:432–438, (September), 1987

Effects of surgical repair on respiratory mechanics in congenital diaphragmatic hernia: H. Sakai, M. Tamura, Y. Hosokawa, et al. J Pediatr 111:432–438, (September), 1987