Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II.

The cause of non-disjunction of chromosome 21 remains largely unknown. Advanced maternal age is associated with both maternal meiosis I (MI) and meiosis II (MII) non-disjunction events. While reduced genetic recombination has been demonstrated in maternal MI errors, the basis for MII errors remains uncertain. We studied 133 trisomy 21 cases with maternal MII errors to test the hypothesis that segregation at MII may also be influenced by genetic recombination. Our data support a highly significant association: MII non-disjunction involves increased recombination that is largely restricted to proximal 21q. Thus, while absence of a proximal recombination appears to predispose to non-disjunction in MI, the presence of a proximal exchange predisposes to non-disjunction in MII. These findings profoundly affect our understanding of trisomy 21 as they suggest that virtually all maternal non-disjunction results from events occurring in meiosis I.

Congenital gastrointestinal defects in Down syndrome: a report from the Atlanta and National Down Syndrome Projects.

We report Down syndrome (DS)-associated congenital gastrointestinal (GI) defects identified during a 15 year, population-based study of the etiology and phenotypic consequences of trisomy 21. Between 1989 and 2004, six sites collected DNA, clinical and epidemiological information on live-born infants with standard trisomy 21 and their parents. We used chi-squared test and logistic regression to explore relationships between congenital GI defects and infant sex, race, maternal age, origin of the extra chromosome 21, and presence of a congenital heart defect. Congenital GI defects were present in 6.7% of 1892 eligible infants in this large, ethnically diverse, population-based study of DS. Defects included esophageal atresia/tracheoesophageal fistula (0.4%), pyloric stenosis (0.3%), duodenal stenosis/atresia (3.9%), Hirschsprung disease (0.8%), and anal stenosis/atresia (1.0%). We found no statistically significant associations between these defects and the factors examined. Although not significant, esophageal atresia was observed more often in infants of younger mothers and Hispanics, Hirschsprung disease was more frequent in males and in infants of younger mothers and blacks, and anal stenosis/atresia was found more often among females and Asians.

Risk factors for nondisjunction of trisomy 21.

The leading cause of Down syndrome (DS) is nondisjunction of chromosome 21 occurring during the formation of gametes. In this review, we discuss the progress made to identify risk factors associated with this type of chromosome error occurring in oogenesis and spermatogenesis. For errors occurring in oocytes, the primary risk factors are maternal age and altered recombination. We review the current progress made with respect to these factors and briefly outline the potential environmental and genetic influences that may play a role. Although the studies of paternal nondisjunction are limited due to the relatively small proportion of errors of this type, we review the potential influence of paternal age, recombination and other environmental and genetic factors on susceptibility. Although progress has been made to understand the mechanisms and risk factors that underlie nondisjunction, considerably more research needs to be conducted to dissect this multifactorial trait, one that has a considerable impact on our species.

Asplenia syndrome in a child with a balanced reciprocal translocation of chromosomes 11 and 20 [46,XX,t(11;20)(q13.1;q13.13)].

We present a 6-year-old girl with a balanced 11;20 translocation [46,XX,t(11;20)(q13.1;q13.13)pat], asplenia, pulmonic stenosis, Hirschsprung disease, minor anomalies, and mental retardation. This case represents the second report of an individual with situs abnormalities and a balanced chromosome rearrangement involving a breakpoint at 11q13. Polymerase chain reaction (PCR) analysis of microsatellite markers excluded uniparental disomy for chromosomes 11 and 20. Segregation analysis of markers in the 11q13 region in the proposita and her phenotypically normal carrier sibs did not show a unique combination of maternal and paternal alleles in the patient. We discuss several possible explanations for the simultaneous occurrence of situs abnormalities and a balanced 11;20 translocation. These include (1) chance, (2) a further chromosome rearrangement in the patient, (3) gene disruption and random situs determination, and (4) gene disruption plus transmission of a recessive or imprinted allele from the mother.

Paternal uniparental disomy in a child with a balanced 15;15 translocation and Angelman syndrome.

Chromosome 15 (15q11-q13) abnormalities cause two distinct conditions, Angelman syndrome (AS) and Prader-Willi syndrome (PWS). We present the first case of a child with a balanced 15;15 translocation and AS in whom molecular studies were crucial in confirming a diagnosis. DNA polymorphisms demonstrated paternal uniparental disomy for chromosome 15, consistent with the diagnosis of AS. The molecular studies also showed the patient to be homozygous at all loci for which the father was heterozygous, suggesting that the structural rearrangement was an isochromosome 15q and not a Robertsonian translocation.

Population-based study of congenital heart defects in Down syndrome.

Mental retardation and hypotonia are found in virtually all Down syndrome (DS) individuals, whereas congenital heart defects (CHDs) are only present in a subset of cases. Although there have been numerous reports of the frequency of CHDs in DS, few of the studies have had complete ascertainment of DS in a defined geographic area. The Atlanta Down Syndrome Project, a population-based study of infants born with trisomy 21, provides such a resource. In the first 6.5 years of the study, 243 trisomy 21 livebirths were identified in the five-county Atlanta area (birth prevalence: 9.6/10,000). Cardiac diagnoses were available on 227 (93%) of the cases and 89% of these evaluations were made by echocardiography, cardiac catheterization, surgery, or autopsy. Of the 227 DS infants, 44% had CHDs including 45% atrioventricular septal defect (with or without other CHDs), 35% ventricular septal defect (with or without other CHDs), 8% isolated secundum atrial septal defect, 7%, isolated persistent patent ductus arteriosus, 4% isolated tetralogy of Fallot, and 1% other. This report is unique in that it contains the largest number of trisomy 21 infants ascertained in a population-based study where modern techniques for diagnosing cardiac abnormalities predominate.

Sucralfate in alleviating post-tonsillectomy pain.

Tonsillectomy results in severe throat pain, ear pain, and trismus until the exposed and inflamed muscle becomes covered with regenerated mucosa. Sucralfate binds with the fibrinous exudate of duodenal ulcers, forming a protective barrier that promotes healing. If a similar buffer could be created in the tonsillar bed, morbidity may be diminished. A double-blind, randomized study was completed in 34 adult patients to determine whether sucralfate, given four times daily for 10 days as a swish and swallow, would significantly reduce postoperative pain and promote healing and recovery. Sucralfate significantly lowered postoperative throat pain, otalgia, and trismus. Sucralfate is a safe and well-tolerated topical agent that offers significant pain reduction and may promote healing in tonsillectomy patients.

Frontal sinus stents.

OBJECTIVES: The formation of scar tissue, synechiae, or osteogenesis in the narrow frontal outflow tract after instrumentation of the frontal sinus has led to attempts to enlarge the frontal duct or stenting. STUDY DESIGN: Prospective pilot study. RESULTS: Sixty-four Freeman frontal sinus stents were used to maintain patency in 46 patients. Stents were inserted using an endoscopic technique in 26 sinuses containing polyps, 20 with pansinusitis, and 18 cavities with stenosis of the frontal duct. External incisions with frontal sinusotomy were required to remove the stenosis and insert the stent in nine sinuses. Polypoid degeneration, granulation, purulent drainage, and lateralization of the middle turbinate were encountered infrequently. Frontal obliteration was subsequently required in six sinuses. CONCLUSION: The Freeman frontal sinus stent prevented blockage of the outflow tract in patients who had removal of disease in the sinus or duct or treatment of frontal stenosis.

Intraoperative radiotherapy of skull base cancer.

As the head and neck surgeon expands the boundaries of resectability into the skull base, the margin of tumor clearance diminishes. Intraoperative radiotherapy (IORT) can be used as an adjunct to skull base surgery and external beam radiation to enhance local control in areas with close margins or remaining microscopic disease. During the period from May 1982 to May 1988, 25 patients underwent IORT of the skull base following resection and prior to closure to treat microscopic disease in 9 patients, sterilize close margins in 14 patients, and attempt to eliminate remaining gross disease in 2 patients. The types of tumors treated were 13 squamous cell carcinomas, 4 adenoid cystic carcinomas, 3 high-grade mucoepidermoid carcinomas, 3 sarcomas, 1 malignant mixed tumor, and an oncocytic adenocarcinoma. The majority of the tumors either originated in the sinuses or were skull base extensions of oral cavity or oropharyngeal cancers. In 22 patients with 1-year follow-up, IORT prevented local recurrence in 14 (64%) patients. This may represent improved control of local disease in patients who historically have a very dismal prognosis. The indications, techniques, and complications of this exciting therapeutic modality are also reviewed.

Utility of preoperative radionuclide scanning for primary hyperparathyroidism.

This study retrospectively reviews 60 cases of primary hyperparathyroidism, 21 of whom underwent technetium 99 sestamibi scanning and 10 of whom underwent thallium 201/technetium 99 pertechnetate scanning preoperatively. The sestamibi and thallium scans demonstrated an 89.5% and a 62.5% sensitivity rate for adenoma, respectively. Neither scan demonstrated hyperplastic glands well. Although the scans localized adenomatous glands to the correct side well, the ability to localize them more discretely was 68.4% and 62.5%, respectively. In cases of solitary adenoma the effect of an accurate preoperative scan on operative time for bilateral exploration was not significant, whereas the experience of the attending surgeon was significant. Also, the cost of the scans at our institution was greater than the cost of the time saved in performing even unilateral neck exploration. Thus preoperative radionuclide scanning is not cost-effective for the initial exploration of patients with primary hyperparathyroidism and is insufficiently sensitive to make routine unilateral neck exploration for adenoma consistently effective.

Management of advanced cervical metastasis using intraoperative radiotherapy.

Seventy-five patients who had advanced cervical metastasis with possible invasion of the deep muscles or carotid artery were approached with aggressive resection and intraoperative radiotherapy (IORT). All metastatic nodes were greater than 3 cm, 65% were fixed on clinical examination, and 35% involved the carotid artery. Forty-six (61%) of the patients had previously received irradiation. Fifteen of the patients required extended neck dissections with carotid resections and grafting. After the resection an average single dose of 2000 cGy of electron beam IORT was delivered. At 2 years, the local control rate within the IORT port was 68% and the absolute survival rate was 45%. Local control rates for close and microscopic margins (76% and 73%, respectively) were significantly better than the control rate for gross residual disease (25%, P < .05). The combination of extended neck dissection, including carotid artery resection if necessary, and IORT appears to offer improved control.

Anterior ischemic optic neuropathy causing blindness in the head and neck surgery patient.

Anterior ischemic optic neuropathy is an uncommon and devastating event that can result in unilateral or bilateral blindness. It has been reported as a complication of ophthalmologic or general surgical and cardiothoracic procedures as well as a spontaneous event in severe systemic disease. Aggravating intraoperative factors include anemia, hemorrhage, hypotension, preexisting small-vessel disease, and increased intraocular pressure. We present a case of anterior ischemic optic neuropathy as a complication in a 48-year-old man undergoing extensive resection of recurrent carcinoma of the head and neck. Possible contributing risk factors in our patient include preexisting hypertension, intraoperative blood loss, previous radical neck dissection with venous compromise, intraoperative head and neck edema, and the use of tightly adherent plastic bubble-type intraoperative eye protection. The possible pathogenesis of this devastating complication and recommendations for prevention and management of anterior ischemic optic neuropathy are described.

Metastasizing pleomorphic adenoma of the nasal septum.

Pleomorphic adenoma is the most common benign tumor of glandular tissue occurring in the head and neck region. There have been several reports of metastasis of this benign-appearing tumor from the salivary glands to distant sites, suggesting hematogenous spread and implantation. Although occurrence of pleomorphic adenoma on the nasal septum has been described, to our knowledge this is the first reported case of recurrent septal pleomorphic adenoma with histologically benign tissue in an enlarged metastatic ipsilateral submandibular lymph node, suggesting lymphatic spread. The literature concerning the subject is reviewed. Wide septal excision and modified neck dissection is the recommended treatment.

Hematoma-induced flap necrosis and free radical scavengers.

Skin flap necrosis due to underlying hematoma can be devastating in reconstructive surgery. The production of free radicals in ischemic tissue and cellular damage caused by them have been well established. Deferoxamine, which is both an iron chelator and a free radical scavenger may have a dual benefit in the pharmacologic manipulation of necrosis in a flap jeopardized by hematoma. Past studies showing the importance of free radical scavengers in improving flap survival in hematoma-induced flap necrosis have used the rat model. The porcine model was used for this study because it is the animal model that most closely resembles human skin. A statistically significant benefit of deferoxamine in reducing necrosis of a skin flap induced by hematoma formation was found. Deferoxamine appears to be promising but requires further investigation before it can be optimally used in human applications.

Intraoperative radiotherapy of head and neck cancer.

Intraoperative radiotherapy (IORT) was developed as an adjuvant to surgery and external beam radiation for aggressive, extensive, or recurrent cancers of the head and neck. This report reviews the indications, technique, response, and complications of IORT. From May 1982 to May 1988, 104 patients received 15 to 20 Gy of radiation delivered through a Lucite cone to areas of high risk of recurrence following resection and prior to closure. The indications for treatment were (1) aggressive primary or recurrent cancer; (2) disease fixed to deep muscle, carotid, or bone; or (3) close margins in an effort to preserve vital structures or function. The IORT was effective in preventing local recurrence in 14 (40%) of 35 patients with 2-year follow-up of squamous cell carcinoma. The complication rate was acceptable. Intraoperative radiotherapy appears to be a safe and beneficial adjunctive therapy for cancers that historically have extremely dismal prognoses.

Communication patterns and decision making among parents and health care providers in the neonatal intensive care unit: a case study.

This case study illustrates salient issues in the communication and decision making of parents in a neonatal intensive care unit. The case provides descriptions that may be typical features of interaction between parents and professionals in a neonatal intensive care unit. Conclusions are drawn from this case with recommendations for practice.

Hemodynamics of cardiac massage.

The introduction of closed chest massage in 1960 initiated a widespread interest in cardiopulmonary resuscitation. Until that time, open chest cardiac massage was the standard for CPR. Initial explanations for blood flow during closed chest CPR were based upon direct compression of the heart. This explanation has given way to demonstrations that blood flows during CPR because of changes in intrathoracic pressure. Changes in intrathoracic pressure that create blood flow have been created by simple maneuvers such as coughing. More involved methods of affecting intrathoracic pressure, in an attempt to improve upon standard closed chest massage, have included applying positive pressure to the airway, binding of the abdomen, and the use of MAST. Cardiac output with closed chest massage is approximately one fourth of normal, and cerebral perfusion is approximately one tenth of normal. Cardiac output with open chest massage is approximately double that obtained by closed chest massage. Cerebral blood flow during open chest massage approaches physiologic values. The use of drugs possessing alpha adrenergic activity and maneuvers that augment intrathoracic pressure improve vital organ perfusion.

Common genitourinary infections.

Vulvovaginal pain, itching, and burning are a triad of symptoms for which women frequently seek health care. Often accompanied by vaginal discharge and dysuria, these symptoms account for as many as 5 million office visits a year. Proper assessment and management of these symptoms by nurses, nurse practitioners, and nurse midwives can help to substantially improve a woman's quality of life and help prevent long-term problems. Several differing syndromes or infections can be the cause of these symptoms. The most common causes are discussed, and a plan for management and prevention is presented.

Management of perimenopausal symptoms.

The perimenopausal period brings about many changes. The significance of many of the signs and symptoms associated with menses also may change. Premenstrual syndrome (PMS) and uterine bleeding need close follow-up during the perimenopausal period. Urinary incontinence appears to worsen because of hormonal changes occurring during the climacteric. All three of these conditions present a special challenge to the health care practitioner.