bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits and Risks of Blood Transfusion in Surgical Patients
Authors: Greenburg A.G.
Published: August 2002

This article attempts to put into a risk‐related perspective modern red blood cell (RBC) transfusion therapy. When making the decision to transfuse, RBCs or blood products, it is important to weigh the risks and benefits of the proposed therapy. It is equally important to evaluate the risk of not transfusing and the morbidity and mortality associated with that decision. After nearly a century of use, RBC transfusions continue to be associated with a variety of risks. Although the initial risks of mismatch and infectious disease transmission are ever decreasing, new risk considerations, particularly immunosuppression, are being uncovered. Because of the nearly universal worldwide fear of transfusion‐related transmission of infectious disease a more conservative transfusion policy has generally taken hold. Transfusion avoidance philosophies and then increased use of autologous RBCs have become commonplace. This article puts a decision‐oriented slant on the risk and benefit of transfusion therapy. The issues behind the inability to discern a defined benefit as well as a commentary on the newly perceived risks is provided. Overall, when increased oxygen delivery is required, the addition of RBCs has an apparent survival benefit in some specific patients. In these patients the risk of transfusion‐related complication is minimized compared to the mortality outcome. For cancer and trauma patients, if transfusion is immunosuppressive and therefore detrimental, alternatives must be considered. The newest question is whether the act of transfusion, independent of the form, allogeneic or autologous, is of itself immunosuppressive.
Uncommon Sites of Hydatid Disease
Authors: Prousalidis J. , Tzardinoglou K. , Sgouradis L. , Katsohis C. , Aletras H.
Published: August 2002

Echinococcosis remains an endemic surgical problem in many Mediterranean countries. We report our experience with such cases when the disease is located in uncommon sites, outside the liver and lungs. This study was an effort similar to a previous one but with more cases and additional information. Between 1967 and 1994 a total of 49 patients suffering from hydatid cysts located in various organs other than the liver and lungs presented to our clinic. There were 28 men and 21 women, with their ages ranging from 10 to 66 years and 22 to 80 years, respectively. Among these patients, 25 had the parasitic cyst in the peritoneal cavity, 10 in the spleen, 5 in the kidney, 3 in the spinal column, 2 in the retroperitoneal space, 1 in the abdominal wall, 1 in the myocardium, 1 in the thoracic wall, and 1 in the thigh. Their hospital stay was 9 to 88 days (average 27 days). Only two patients—one with cardiac hydatidosis and one with spinal hydatidosis—died postoperatively. Three patients with multiple cysts in the peritoneum and one with cysts in the thigh had recurrences of the disease and were reoperated successfully.
Effect of Duodenal Distension on the Pyloric Sphincter and Antrum and the Gastric Corpus: Duodenopyloric Reflex
Authors: Shafik Ahmed
Published: August 2002

The mechanical effect of balloon distension of the duodenum on the stomach was studied in 10 mongrel dogs with a mean weight of 14.8 ± 3.2 kg. The response of the pyloric sphincter and antrum as well as of the corpus of the stomach to duodenal distension by a balloon filled with water in increments of 2 ml, up to 6 ml, was determined. The test was repeated after anesthetizing the pyloric sphincter and antrum and the duodenum, each at a separate time. In 5 of 10 dogs the effect of duodenal distension on the vagotomized stomach was studied. Duodenal distension with 2 ml of water produced an increase in the pyloric sphincter pressure (p < 0.05) and a decrease in the antral pressure (p < 0.05); it had no effect on corporeal pressure (p > 0.05). Distension with 4 ml and 6 ml produced the same effect as 2 ml (p > 0.05). The anesthetized pyloric sphincter and antrum did not respond to duodenal distension. Likewise, the pyloric sphincter and antrum showed no response to distension of the anesthetized duodenum or of the duodenum after vagotomy. Pyloric sphincter contraction and antral dilatation upon duodenal distension suggest a reflex relation we call the duodenopyloric reflex. This reflex appears to prevent duodenopyloric reflux. Moreover, the antrum dilates probably to accommodate more gastric contents.
Intraoperative Insulin Measurement during Surgical Management of Insulinomas
Authors: Proye Charles , Pattou François , Carnaille Bruno , Lefebvre Jean , Decoulx Marc , d’Herbomez Michèle
Published: August 2002

Intraoperative hormonal measurements have been used successfully to guide the surgical treatment of various endocrine diseases. In this study, we report the results of intraoperative insulin measurement (IIM) in patients with organic hypoglycemia. IIMs were performed during 52 operations in 51 patients. Hyperinsulinism was secondary to a sporadic insulinoma (M= 40), a type I multiple endocrine neoplasia (MEN‐I) (M= 8), an insulin‐secreting carcinoma (M= 1), or pancreatic nesidioblastosis (M= 2). The insulin was measured with a radioimmunologic assay in blood samples simultaneously drawn from a peripheral vein and the portal vein at the beginning of the operation (T1) and 20 minutes after tumor removal (T2). Normoglycemia was achieved after surgery in 50 cases (96%). Systemic and portal insulin levels were normal at T1 in eight patients, precluding any further interpretation of the test. Completeness of surgery was confirmed by normalization of both systemic and portal insulin levels at T2 in 36 patients. In seven cases the systemic or portal insulin levels (or both) remained elevated at T2 despite a favorable outcome after surgery. Failure of the surgical procedure was predicted in two patients by the persistence of high levels of insulin at T2. In patients with initially elevated serum insulin levels, the positive predictive value and the specificity of intraoperative insulin measurement for completeness of surgery were both 100%. The sensitivity was 84%, the negative predictive value 22%, and the accuracy of the test 84%. We concluded that IIM is a simple, highly reliable tool for predicting the completeness of surgery in patients with organic hypoglycemia. IIM appears to be a valuable addendum to the surgical armamentarium against insulinoma especially for patients with atypical causes, such as MEN, insulin‐secreting carcinoma, or pancreatic nesidioblastosis.
Are There Indications for Palliative Resection in Pancreatic Cancer?
Authors: Gouma D.J. , van Dijkum E.J.M. Nieveen , van Geenen R.C.I. , van Gulik T.M. , Obertop H.
Published: August 2002

Controversy exists about the indication for a palliative pancreatoduodenectomy. A palliative resection for patients with a pancreatic carcinoma can be performed safely nowadays with low mortality and acceptable morbidity in centers with experience. The early results in terms of mortality and morbidity are not different from resections with curative intent or even after bypass surgery. The procedure seems effective for controlling symptoms of the disease, and the quality of life after a palliative resection is acceptable and not worse than after bypass surgery. It is, however, still doubtful whether the incidence of symptom recurrence, such as jaundice, obstruction, and pain, is lower after resection than after bypass surgery. The longer survival after palliative resection could also be due to patient selection and postoperative treatment. There are no randomized trials to prove the superiority of palliative resection over bypass surgery. The safety of pancreatic resection for cancer has already changed the policy in centers with experience, and surgeons are more willing to perform a resection because the results are better or at least the same as after bypass surgery. There are, however, no results to confirm that a palliative resection should be performed routinely or to justify resection as a debulking procedure.
Clinical Trials
Authors: Kestle John R. W.
Published: August 2002

The randomized clinical trial (RCT) is often referred to as the gold standard for the assessment of treatment efficacy. RCTs are receiving greater attention in the literature and higher priority by funding agencies than they have in the past. In this paper, the basic principles of clinical trial design are reviewed using examples from the neurosurgical literature. The importance of designing the trial to answer one question well is emphasized.
Prospective Study of Gastric Outlet Obstruction in Unresectable Periampullary Adenocarcinoma
Authors: Shyr Yi‐Ming , Su Cheng‐Hsi , Wu Chew‐Wun , Lui Wing‐Yiu
Published: August 2002

Controversy persists regarding the role of prophylactic gastrojejunostomy in patients with unresectable periampullary adenocarcinoma. In review of the retrospective series, presence of gastric outlet obstruction (GOO) has been claimed to be a bad prognostic sign. This prospective study aimed to clarify the necessity of routine prophylactic gastrojejunostomy in patients with unresectable periampullary adenocarcinoma. The incidence and prognostic significance of GOO were also evaluated. Sixty‐six patients with unresectable periampullary adenocarcinoma were enrolled. They were divided into 2 groups to receive either a single biliary bypass or a double bypass (concomitant gastric and biliary bypasses) if they had GOO. The single bypass group was followed up to assess the incidence of GOO and subsequent need of a gastric bypass. Prognostic factors were evaluated by univariate and multivariate analyses. Forty‐four (67%) of the overall 66 patients presented with GOO at the time of diagnosis. There was no statistical difference regarding the morbidity and mortality between the 2 groups, except longer (7 days) hospital stay in the double bypass group. Seven (31.8%) of the 22 patients in the single bypass group subsequently developed GOO an average of 6.2 ± 1.0 months after their initial biliary bypass. By univariate analysis, significant prognostic factors for unresectable periampullary adenocarcinoma were: GOO (p= 0.0379), pancreatic head origin (p= 0.0146 by univariate analysis), and distant metastasis (p < 0.0001). After multivariate analysis, only pancreatic head origin and distant metastasis remained significant independent factors of poor prognosis. In conclusion, gastrojejunostomy should be performed prophylactically in addition to a biliary bypass in patients with unresectable periampullary adenocarcinoma. The presence of GOO is not an independent factor of poor prognosis, but a reflection of the aggressive biologic behavior of pancreatic head adenocarcinoma.
Asynchronization of local population dynamics and persistence of a metapopulation: a lesson from an endangered composite plant, Aster kantoensis
Authors: Shimada M. , Ishihama F.
Published: August 2002

Fragmentation of a large habitat makes local populations less linked to others, and a whole population structure changes to a metapopulation. The smaller a local population is, the more strengthened extinction factors become. Then, frequent extinctions of local populations threaten persistence of the metapopulation unless recolonizations occur rapidly enough after local extinctions. Spatially structured models have been more widely used for predicting future population dynamics and for assessing the extinction risk of a metapopulation. In this article, we first review such spatially structured models that have been applied to conservation biology, focusing on effects of asynchronization among local population dynamics on persistence of the whole metapopulation. Second, we introduce our ongoing project on extinction risk assessment of an endangered composite biennial plant, Aster kantoensis, in the riverside habitat, based on a lattice model for describing its spatiotemporal population dynamics. The model predicted that the extinction risk of A. kantoensis depends on both the frequency of flood occurrence and the time to coverage of a local habitat by other competitively stronger perennials. Finally, we present a measure (Hassell and Pacala's CV2) for quantifying the effect of asynchronization among local population dynamics on the persistence of a whole metapopulation in conservation ecology.
Hepatic lobe torsion in 3 dogs and a cat
Authors: Swann Heather M. , Brown Dorothy Cimino
Published: August 2002

Objective—To describe the clinical features of hepatic lobe torsions in 3 dogs and 1 cat.

Study Design—Retrospective clinical study.

Animals—Three client‐owned dogs and 1 client‐owned cat.

Methods—Medical records were reviewed, and information regarding signalment, clinical signs, physical‐exam findings, diagnostic tests performed, treatment, outcome, and follow‐up was retrieved.

Results—Clinical signs existed for 4 hours to 1 week before examination. Signs were nonspecific in 2 animals that did not have an obvious cause for the hepatic torsion. These signs consisted of lethargy (2), polyuria/polydypsia (2), and anorexia (1). In the other 2 animals, signs were suggestive of the underlying cause of the hepatic lobe torsion. In 1 dog, the torsion was associated with a traumatic diaphragmatic hernia. The cat had a concurrent hemoabdomen secondary to a ruptured hepatocellular carcinoma. Bloodwork abnormalities were nonspecific. Twisted liver lobes included the left lateral lobe (2), the caudate lobe (1), and the right medial lobe (1). Surgical resection (2) or repositioning (1) of the affected liver lobe was attempted in the 3 dogs, and was successful in 2.

Conclusions—Hepatic lobe torsion is a rare problem but has been reported in humans, rabbits, dogs, pigs, a cat, and a horse. The left lateral liver lobe is most frequently affected. This condition may be idiopathic or associated with neoplasia or absence of ligamentous support (congenital or traumatic) to the liver.

Clinical Relevance—Prompt surgical resection or repositioning of the involved liver lobe can lead to a successful outcome, avoiding the deleterious effects of venous obstruction such as thrombosis and subsequent necrosis.
Analysis of Factors Affecting Survival in Dogs With Aortic Body Tumors
Authors: Ehrhart Nicole , Ehrhart E. J. , Willis Jennifer , Sisson David , Constable Peter , Greenfield Cathy , Manfra‐Maretta Sandra , Hintermeister John
Published: August 2002

Objective—To evaluate the effect of perioperative and operative variables on survival time in dogs with aortic body tumors.

Study Design—Retrospective study.

Sample Population—Twenty‐four client‐owned dogs with histologically confirmed aortic body tumor.

Methods—Seventy‐eight patient records of dogs seen at the University of Illinois Veterinary Teaching Hospital between 1989 and 1999 with a diagnosis of a heart‐base mass were reviewed. Dogs without histologic conformation of an aortic body tumor were excluded. Age; sex; breed; the presence of pleural effusion, pericardial effusion, or abdominal effusion; evidence of cardiac arrhythmias; evidence of distant metastasis; treatment with pericardectomy; treatment with chemotherapy; and time from diagnosis until euthanasia or death were recorded on a spreadsheet. Cox proportional‐hazard ratios were used to calculate the relationship of risk variables to survival time. Median survival time was determined using life‐table analysis.

Results—Twenty‐four dogs met the criteria for inclusion in the study. The median age of dogs with aortic body tumors was 9 years. All dogs had a surgical biopsy performed. Fourteen dogs had a pericardectomy at the time of the biopsy procedure. Of all factors analyzed, only treatment with pericardectomy had a significant influence on survival (P= .0029). Dogs that had pericardectomy survived longer (median survival, 730 days; range, 1–1,621 days) compared with dogs that did not have pericardectomy (median survival, 42 days; range, 1–180 days). This finding was independent of the presence or absence of pericardial effusion at the time of surgery.

Clinical Relevance—Dogs that are diagnosed with aortic body tumors may benefit from a pericardectomy at the time of surgical biopsy.
Use of palladium catalysis in the synthesis of novel porphyrins and phthalocyanines
Authors: SHARMAN W. M. , LIER J. E. VAN
Published: August 2002

Palladium catalysts offer a rich and highly versatile chemistry for the synthesis of novel porphyrins and phthalocyanines. These mild and flexible reactions have been used extensively in the preparation of interesting porphyrins and phthalocyanines, either in the synthesis of substituted precursors or in the modification of pre-existing macrocycles. For these tetrapyrrolic compounds, metal-mediated reactions such as these offer extensive benefits, which have been taken advantage of in order to add novel substituents, synthesize naturally occurring molecules and prepare multi-macrocyclic arrays. This review gives an overview of the use of palladium catalysts in the synthesis of porphyrins and phthalocyanines along with the applications of some of the compounds prepared.
An Update on Transformational Learning
Authors: Baumgartner Lisa M.
Published: August 2002

Andragogy and self‐directed learning continue to be important to our present‐day understanding of adult learning.
Innovation in the food industry
Authors: Traill W. Bruce , Meulenberg Matthew
Published: August 2002

Twelve food‐manufacturing companies in six European countries have been studied with respect to the way in which they innovate, their motivations, and their emphasis on product or process innovation. It is suggested that the traditional “demand‐pull” versus “technology‐push” versus “a mixture of both” debate is too simplistic. Firms behave differently depending on their dominant “orientations” towards the product, the process, or the market, the types of market they supply (particularly whether they supply branded or private‐label products), the nature of their ownership (public, private, co‐operative), market size and scope, and company size. The suggestions of the case studies are, in general, supported by quantitative results from a survey of food manufacturers, though the survey was not designed specifically for this purpose and further quantitative model development is proposed. The findings reported in this article and the proposed refinements are important to firms and policy‐makers concerned with the efficiency and effectiveness of food industry innovation [JEL Classification Codes: L100, L200, L660] © 2002 Wiley Periodicals, Inc.
Treatment of sinus histiocytosis with massive lymphadenopathy (rosai‐dorfman disease): Report of a case and literature review
Authors: Pulsoni Alessandro , Anghel Gabriel , Falcucci Paolo , Matera Roberta , Pescarmona Edoardo , Ribersani Michela , Villiva' Nicoletta , Mandelli Franco
Published: August 2002

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder of unknown etiology, usually associated with lymph node enlargement in various superficial or deep sites. It usually shows a prolonged clinical course with occasional exacerbation and remission phases. We describe the long‐term follow‐up of a case of SHML that showed typical clinical features and in which various therapeutic strategies were attempted. Chemotherapy and α‐interferon (IFN) were ineffective; surgery was ultimately required with satisfactory results. From an extensive literature review we found different treatment strategies in SHML in the 80 cases published between 1969 and 2000. Spontaneous resolution of adenopathies is frequently observed: 32 out of 40 cases which did not receive chemotherapy, radiotherapy, or surgery were healthy at the time of publication. Radiotherapy alone showed conflicting results: 3 complete remissions (CR) were obtained in the 9 patients treated. Surgical debulking when required was effective—8/9 CR—while chemotherapy showed generally negative results. IFN has been previously employed in only one case. In conclusion, clinical observation without treatment is advisable when possible. In the presence of vital organ compression and/or extranodal localization with important clinical signs, surgical debulking may be necessary. Radiotherapy has shown limited efficacy, while chemotherapy is in general ineffective. More experience is needed to evaluate the role of IFN. Am. J. Hematol. 69:67‐71, 2002. © 2002 Wiley‐Liss, Inc.
Hypothermia‐induced platelet aggregation in heparinized flowing human blood: Identification of a high responder subpopulation
Authors: Hall Matthew W. , Goodman Paul D. , Alston Steven M. , Solen Kenneth A.
Published: August 2002

Cold‐induced platelet aggregation (CIPA) in PRP has previously been documented in connection with platelet preservation (4–15°C). This report describes hypothermia‐induced platelet aggregation (HIPA) in whole blood and at temperatures used in open‐heart surgery (24–32°C). HIPA (specifically, the formation of occlusive aggregates) was studied in human whole blood. Fresh heparinized (1.5 U/ml) human blood was cooled and maintained at target temperatures (15, 20, 24, 28, 32, or 37°C) as it flowed (1 ml/min) through 75‐cm long 1/32″ internal diameter polymer conduit. The formation of aggregates in the tubing was verified using optical video microscopy and was quantified by a light‐scattering method and a constant‐pressure filtration method. Donors were tested at least twice at each target temperature and were classified into three separate response regimes (Low, Medium, and High) on the basis of the number of aggregates and the duration of their appearance. The screening of 121 donors (average age 22.3 ± 4.3 years) for HIPA at 24°C (the temperature of maximum response) indicated 14% High Responders, 18% Medium Responders, and 68% Low Responders. HIPA was inhibited by EDTA, citrate, PGE1, and Tirofiban, but not by aspirin, and it was enhanced by elevated heparin levels. HIPA was consistently noted in the blood of a subpopulation of donors, and the associated platelet aggregates in the blood of High Responders were rigid and occlusive. It is postulated that such aggregates may contribute to cognitive dysfunction noted in patients undergoing hypothermic open‐heart surgery, and that postulus is being investigated. Am. J. Hematol. 69:45–55, 2002. © 2002 Wiley‐Liss, Inc.
Early onset of acute immune‐mediated lung injury in a child undergoing allogeneic peripheral blood transplantation
Authors: Sevilla Julián , González‐Vicent Marta , Madero Luis , González‐Mediero Imelda , Díaz Miguel A.
Published: August 2002

Animal models have recently clarified the lung injury after allogeneic hematopoietic transplantation. These works have confirmed the role of donor T lymphocytes in immune‐mediated inflammatory reactions in the lung. We report here a fatal case of a 3‐year‐old child who developed acute respiratory failure coinciding with the onset of hyper‐acute graft versus host disease (aGVHD) after allogeneic peripheral stem cell transplantation. aGVHD was refractory to treatment and the patient died on day +28. Lung necropsy showed interstitial pneumonia and peribronchial and perivascular infiltration by mononuclear cells, with no viral inclusions. These findings are not specific but have been found by some authors in animal models with acute immune‐mediated lung injury related with donor T lymphocytes. Immune‐mediated lung injury, as defined by animal models, should be considered in patients with severe signs of systemic aGVHD while excluding other known etiologies of pulmonary disease. Am. J. Hematol. 69:56‐58, 2002. © 2002 Wiley‐Liss, Inc.
Autoimmune hemolytic anemia
Authors: Gehrs Bradley C. , Friedberg Richard C.
Published: August 2002

Red blood cell (RBC) autoantibodies are a relatively uncommon cause of anemia. However, autoimmune hemolytic anemia (AIHA) must be considered in the differential diagnosis of hemolytic anemias, especially if the patient has a concomitant lymphoproliferative disorder, autoimmune disease, or viral or mycoplasmal infection. Classifications of AIHA include warm AIHA, cold agglutinin syndrome, paroxysmal cold hemoglobinuria, mixed‐type AIHA, and drug‐induced AIHA. Characteristics of the autoantibodies are responsible for the various clinical entities. As a result, diagnosis is based on the clinical presentation and a serologic work‐up. For each classification of AIHA, this review discusses the demographics, etiology, clinical presentation, laboratory evaluation, and treatment options. Am. J. Hematol. 69:258–271, 2002. © 2002 Wiley‐Liss, Inc.
Severe hypophosphatemia: A rare cause of intravascular hemolysis
Authors: Melvin Jennifer D. , Watts Raymond G.
Published: August 2002

A 3‐year‐old child presented with severe hyperphosphatemia (phosphate 45 mg/dL) secondary to chronic enema use. Following aggressive correction of the hyperphosphatemia, hypophosphatemia ensued (phosphate 1.7 mg/dL). Concurrently, the patient developed severe intravascular hemolysis and RBC morphologic defects. The hemolysis and morphologic defects corrected with return to normal serum phosphate levels. Severe hypophosphatemia is a rare cause of intravascular hemolysis. Am. J. Hematol. 69:223–224, 2002. © 2002 Wiley‐Liss, Inc.
Therapeutic choices for patients with hemophilia and high‐titer inhibitors
Authors: Kulkarni Roshni , Aledort Louis M. , Berntorp Erik , Brackman Hans H. , Brown Deborah , Cohen Alan R. , Ewing Nadia P. , Gringeri Alessandro , Gruppo Ralph , Hoots Keith , Leissenger Cindy , Peerlinck Katheliijne , Poon Man‐Chiu , Wong Wing‐Yen
Published: August 2002

Effective treatment of bleeding episodes in hemophilia with high titer inhibitors (HTI) remains a challenge, despite the fact that the therapeutic armamentarium has expanded considerably over the past few years. Treatment safety has improved with the availability of porcine factor VIII (FVIII) and bypassing products such as recombinant factor VIIa (rFVIIa), and plasma‐derived activated Prothrombin Complex Concentrates (aPCCs) that are virally inactivated. The major drawbacks of rFVIIa and aPCCs are their unpredictable hemostatic effect, lack of laboratory assays to monitor efficacy and dosing frequency, and the risk of thrombosis. The proceedings of a one‐day workshop of physicians who specialized in treating patients with hemophilia held in Vienna on May 13, 2000 have been summarized. In making a decision regarding the choice of product, physicians often consider the type of bleeding episode (life or limb threatening), age of the patient, volume of the reconstituted product, previous exposure to plasma derived products, cost, efficacy, and safety. For plasma naïve patients, to achieve rapid hemostasis a majority of the panelists used porcine FVIII (for patients who lack porcine inhibitory antibodies) or rFVIIa. For patients previously treated with plasma derived factors, in addition to the above concentrates, aPCCs were recommended. Although no data exists regarding safety and efficacy, switching products was routinely practiced either because of availability or cost. Furthermore, the panelists were uncertain about the efficacy of bypassing agents in the prevention of joint disease in inhibitor patients. The workshop participants felt that future research offers the best solution to resolve some of the dilemmas faced by clinicians and may help individualise treatment in a hemophilia patient with a high titer inhibitor. Am. J. Hematol. 67:240–246, 2001. © 2001 Wiley‐Liss, Inc.
Spectrum of β‐thalassemia in Jordan: Identification of two novel mutations
Authors: Sadiq M.F. , Eigel A. , Horst J.
Published: August 2002

Two hundred and forty‐four β‐thalassemia alleles were identified from 135 unrelated occasionally and periodically transfusion dependent β‐ and S/β‐thalassemia patients from all regions of Jordan. Allele identification was achieved by PCR amplification of β‐globin genes, dot‐blotting the amplified DNA, hybridization with allele specific synthetic probes, and direct sequencing of amplified genomic DNA. A total of 19 different mutations were detected, eight of them constituted about 86% of the Jordanian thalassemic chromosomes. These mutations were IVS1‐110 (G>A) (25%), IVS2‐1 (G>A) (15%), IVS2‐745 (C>G) (14.2%), IVS1‐1 (G>A) (10%), IVS1‐6 (T>C) (8.3%), codon 37 (G>A) (6.3%), codon 39 (C>T) (4.6%), and codon 5 (‐C) (3.8%). The remaining eleven mutations were rare, presented with frequencies ranging between 0.4% and 1.6%. These included two novel mutations and four others detected in Jordan for the first time. The novel mutations were the frame shift (‐C) at codon 49 and the substitution (A>C) at position −29 in the TATA box. Four alleles (1.6%) remained unidentified; having no abnormalities in their β‐globin gene sequences and therefore, constituted additional defects causing β‐thalassemia in the Jordanian population. These unknown alleles are expected to be candidates for upstream or downstream mutations affecting the expression of β‐globin gene. The results provided the essential foundation for planning a national preventive program for thalassemia in Jordan and will help improving the medical services for the patients and their families by helping their clinicians and genetic counselors in evaluating their variants and designing their treatment regimens. Am. J. Hematol. 68:16–22, 2001. © 2001 Wiley‐Liss, Inc.
Are there ethnic differences in sleep architecture?
Authors: Profant Judi , Ancoli‐Israel Sonia , Dimsdale Joel E.
Published: August 2002

The possibility of ethnic differences in sleep architecture was initially examined in conjunction with studies of sleep apnea (study 1). This possibility was then examined in another cohort of patients to determine whether the results might generalize (study 2). Polysomnography was obtained in both cohorts as part of larger protocols investigating sympathetic nervous system activity, blood pressure, and sleep. Sleep monitoring took place in an inpatient clinical research center of a university hospital. Study 1 focused on sleep apnea physiology and involved volunteers with sleep apnea who were otherwise healthy. Study 2 focused on differences in stress reactivity between American Black and White subjects and involved hypertensive and normotensive volunteers who were otherwise healthy. Analyses include 61 participants from study 1 and 35 participants from study 2. Ethnicity in both cohorts was determined by self‐report. Participants in both studies were monitored during sleep with traditional polysomnography including electroencephalography (EEG), electromyography (EMG), electrooculography (EOG), and oximetry. In Study 1, Blacks had longer TST (P < 0.01), more REM sleep (P < 0.05), and less WASO (P < 0.05) than Whites. After controling for RDI, Blacks had longer TST and spent a smaller percentage of time in deep sleep (P < 0.05). In study 2, Blacks had longer TST and REM sleep, lower percent deep sleep, and lower percent deep sleep controling for RDI (P < 0.05). In two separate studies, Blacks had longer TST, more minutes of REM, and lower percentage deep sleep. These findings suggest possible ethnic differences in sleep architecture. Am. J. Hum. Biol. 14:321–326, 2002. © 2002 Wiley‐Liss, Inc.
Infants thinner at birth exhibit smaller kidneys for their size in late gestation in a sample of fetuses with appropriate growth
Authors: Lampl Michelle , Kuzawa Christopher W. , Jeanty Philippe
Published: August 2002

Fetal ultrasound measurements were employed to investigate the relationship between weight and ponderal index at birth and kidney size during the second (23 weeks) and third (32 weeks) trimesters of pregnancy in a sample of 25 normally growing fetuses. Kidney volume and kidney volume / fetal weight ratio at 32 weeks are significantly and positively related to both weight and ponderal index at birth, controlling for sex, gestational age at birth, and day of ultrasound measurement. A second‐degree polynomial relationship approximates the predictability of kidney volume fetal weight ratio at 23 weeks to that at 32 weeks, demonstrating shifting growth rates in fetal organ and body growth relationships during midgestation. Sex and parental size are suggested as contributing to these patterns. Females have a surge in renal growth between 23 and 32 weeks to catch up to earlier growing males, and maternal weight significantly predicts incremental growth in kidney volume and the kidney volume / fetal weight ratio at 32 weeks of gestation. The observation that fetuses relatively thin at birth have relatively smaller kidneys for their size in late gestation suggests that the influence of maternal weight on birth outcome may act through organ growth. Am. J. Hum. Biol. 14:398–406, 2002. © 2002 Wiley‐Liss, Inc.
Child factor in measurement dependability
Authors: Lampl Michelle , Birch Leann , Picciano Mary Frances , Johnson Michael L. , Frongillo Edward A.
Published: August 2002

A primary consideration in longitudinal growth studies is the identification of growth from error components. While previous research has considered matters of measurement accuracy and reproducibility in detail, few reports have investigated the errors of measurement due to aspects of the physiology and cooperation of the child. The present study directly assesses this source of measurement undependability for the first time. Investigation of total measurement error variance in 925 recumbent length replicates taken over stasis intervals in growth identifies that between 60% and 70% of total measurement unreliability is due to a child factor undependability. Individual differences are significant and longitudinal growth analyses should consider two to three times the technical error of measurement statistic as a reasonable estimate of the total unreliability for any single measurement of an infant's recumbent length. These results raise issues regarding analytic methods as applied to serial growth data. Am. J. Hum. Biol. 13:548–557, 2001. © 2001 Wiley‐Liss, Inc.
Transmission disequilibrium studies of the serotonin 5‐HT2A receptor gene (HTR2A) in autism
Authors: Veenstra‐VanderWeele Jeremy , Kim Soo‐Jeong , Lord Catherine , Courchesne Rachel , Akshoomoff Natasha , Leventhal Bennett L. , Courchesne Eric , Cook Edwin H.
Published: August 2002

Hyperserotonemia in autism is one of the longest‐standing biochemical findings in a psychiatric disorder. This well‐replicated finding and subsequent studies of platelet serotonin receptors in autism indicate that the serotonin 2A receptor gene (HTR2A) on chromosome 13q is a primary candidate gene in autism. Converging data from recent genome screens also implicates the genomic region containing HTR2A. Based on these lines of evidence, the transmission/disequilibrium test (TDT) was used to assess transmission disequilibrium between autism and haplotypes of three polymorphisms, including the promoter ‐1438 G/A single nucleotide polymorphism (SNP) in perfect linkage disequilibrium with the 102 T/C SNP in previous studies, a newly identified SNP in intron 1 near exon 2, and the SNP responsible for the His452Tyr amino acid change in exon 3. Because expression studies have shown HTR2A to be polymorphically imprinted in the brain, secondary analyses were split into maternal and paternal transmissions. No evidence was found for unequal transmission of haplotypes; however, power analysis reveals low power to detect a parent‐of‐origin effect in this sample size. © 2002 Wiley‐Liss, Inc.
De novo interstitial direct duplication 1(q23.1q31.1) in a fetus with Pierre Robin sequence and camptodactyly
Authors: Aboura A. , Coulomb‐L'Herminé A. , Audibert F. , Capron F. , Frydman R. , Tachdjian G.
Published: August 2002

Interstitial duplications of chromosomal region 1q are rarely seen. We report the first prenatal diagnosis of pure partial trisomy 1q. The fetus was karyotyped for polyhydramnios, micrognathia, and flexion of fingers of both hands. Conventional and molecular cytogenetics showed a de novo direct duplication of the chromosomal region 1q23.1q31.1 leading to a partial trisomy 1q. At autopsy, the fetus showed Pierre Robin sequence (PRS) and camptodactyly. The main histological finding was a decreased number of motoneurons with apoptotic features in the anterior horn of the spinal cord. A literature review and our observations suggest that genetic material mapping to chromosome 1q25 could be responsible for PRS with distal arthrogryposis when this is in triple dose. © 2002 Wiley‐Liss, Inc.
Phenotypic variation in Melnick‐Needles syndrome is not reflected in X inactivation patterns from blood or buccal smear
Authors: Kristiansen Marianne , Knudsen Gun Peggy , Søyland Anne , Westvik Jostein , Ørstavik Karen Helene
Published: August 2002

Melnick‐Needles syndrome is a rare putative X‐linked dominant bone dysplasia. The patients have short stature, characteristic facial features, and a normal intelligence. The skeletal dysplasia includes S‐shaped curvature of tubular bones and sclerosis of the base of the skull. The phenotype of affected individuals varies, even within families. This could be related to X chromosome inactivation. We report here on a very mildly affected mother and her two severely affected daughters with characteristic features of Melnick‐Needles syndrome. In addition, the two daughters had very similar pigmented nevi on their back. X chromosome inactivation analysis of blood DNA revealed a skewed X inactivation pattern in all three affected females, with the normal X chromosome as the predominating active X chromosome. The X inactivation pattern was similar in buccal smear and blood DNA in the mother and one of the daughters, whereas the other daughter had a skewed pattern in blood only. X chromosome inactivation in blood and buccal smear DNA therefore does not explain the phenotypic variation in this family. The skewed X chromosome inactivation is in agreement with X‐linked inheritance of Melnick‐Needles syndrome and suggests a critical role of the Melnick‐Needles gene in hematopoietic cell proliferation. Clinical evidence indicates that Melnick‐Needles syndrome is allelic to the otopalatodigital syndromes, which have been assigned to Xq26‐28. Haplotype analysis of the X chromosomes in this family was in agreement with the localization of the gene for Melnick‐Needles syndrome to Xq25‐qtel. © 2002 Wiley‐Liss, Inc.
Unique case of mosaicism involving two morphologically similar marker chromosomes of different centric origin in a patient with developmental delay
Authors: Levy Brynn , Jalal Syed M. , Dunn Teresa M. , Warburton Peter E. , Tonk Vijay S. , Hirschhorn Kurt , Lockhart Lillian H. , Hughes T. , Velagaleti Gopalrao V.N.
Published: August 2002

A five‐year‐old Caucasian male presented with developmental delay, minor dysmorphic features, and hyperactivity. Cytogenetic analysis showed the presence of a marker chromosome in the majority of cells analyzed. Fluorescence in situ hybridization (FISH) analyses using several alpha satellite probes, including D13Z1/D21Z1, did not reveal any signal on the marker chromosome. Subsequent multicolor FISH (M‐FISH) indicated the marker to be derived from chromosome 13, and FISH with a chromosome 13 paint confirmed this finding. The absence of D13Z1/D21Z1 signal on the marker suggested that it was analphoid in nature. Comparative genomic hybridization (CGH) was utilized to further characterize the region of chromosome 13 from which the marker originated, and unexpectedly revealed a gain of chromosomal material at both the centromeric regions of chromosomes 3 and 13. In view of the CGH results, extensive FISH studies with D3Z1 and D13Z1/D21Z1 were performed and revealed the presence of four cell lines comprising one normal cell line (50.5%), a cell line with a chromosome 3 derived marker (19%), a cell line containing a marker derived from chromosome 13 (20%), and a cell line with both markers (10.5%). As the two markers appeared morphologically similar by GTG banding, all 47,XY metaphases in the initial analysis were thought to comprise only a single marker. This is the first report, to our knowledge, of the presence of a chromosome 3 and a chromosome 13 marker in mosaic condition in a congenital disorder. In light of our experience, we urge caution in interpreting karyotypes with marker chromosomes. Our case illustrates the limitations of fluorescent DNA probes and sampling errors. © 2002 Wiley‐Liss, Inc.
Potentially functional polymorphism in the promoter region of prodynorphin gene may be associated with protection against cocaine dependence or abuse
Authors: Chen Andrew C.H. , LaForge K. Steven , Ho Ann , McHugh Pauline F. , Kellogg Scott , Bell Kathy , Schluger Rosemary P. , Leal Suzanne M. , Kreek Mary Jeanne
Published: August 2002

It has been demonstrated that the opioid peptide dynorphin plays a role in modulating responses to several psychoactive substances including cocaine. Our laboratory and others have found that mRNA levels of dynorphin in the caudate and putamen are elevated after acute or chronic cocaine exposure in rats. Recently, a 68‐base pair (bp) repeat polymorphism within the core promoter region of the human prodynorphin gene has been reported to occur in alleles containing one, two, three, or four copies. This repeat contains a putative AP‐1 transcription factor binding site; reporter gene constructs with three or four, but not one or two, copies of the tandem repeats were shown to be associated with increases in transcriptional activation in in vitro cellular assays. We hypothesize that this polymorphism may be associated with individual differences in vulnerability to cocaine dependence or abuse. From an ongoing study of the genetics of addiction, 174 subjects were studied, including individuals with a primary diagnosis (DSM‐IV criteria) of cocaine dependence (N = 61) or abuse (N = 22), and controls with no history of any substance dependence or abuse (N = 91). We designed primers for polymerase chain reaction (PCR) to amplify sequences of the promoter region of the prodynorphin gene containing the repeat element. The association of alleles containing three or four repeats with cocaine dependence/abuse was examined. With data stratified by ethnic group, pooled relative risk (RR) with Mantel‐Haenszel Chi square was calculated: RR = 0.59 (95% confidence interval 0.37–0.95), χ2(1) = 4.14, P = 0.042. Our results suggest that this allelic variation at the promoter region of the prodynorphin gene (alleles with three or four repeats), which may result in enhanced transcription of the gene, may contribute to relative protection and decrease individual vulnerability to develop cocaine dependence or abuse. © 2002 Wiley‐Liss, Inc.
Identification of three polymorphisms in the translated region of PLC‐γ1 and their investigation in lithium responsive bipolar disorder
Authors: Ftouhi‐Paquin Nouzha , Alda Martin , Grof Paul , Chretien Nathalie , Rouleau Guy , Turecki Gustavo
Published: August 2002

Recently, we have found an association between bipolar disorder patients who are excellent responders to lithium prophylaxis and a polymorphic marker located in the first intron of the phospholipase C‐γ1 gene (PLC‐γ1) [Turecki et al., 1998: Mol Psychiatry 3:534‐538]. As this variant is not known to be functional, we searched for other markers within the coding region, using single‐strand conformational polymorphism (SSCP) analysis. We have identified three polymorphic sites localized in three different exons of the PLC‐γ1 gene (exons 9, 26, 31). Variation studies of these potentially functional sites in a group of 133 bipolar patients with an excellent response to lithium prophylaxis and a comparison group of 99 healthy controls showed no difference in genotype distributions for exon 9 (chi‐square = 1.41, df = 2, P = 0.49), exon 26 (chi‐square = 2.26, df = 2, P = 0.13), or exon 31 (chi‐square = 1.41, df = 2, P = 0.49). Similar results were observed for allele distributions. These results suggest that our previous findings were not the result of linkage disequilibrium with these variants. © 2001 Wiley‐Liss, Inc.
Incorporating language phenotypes strengthens evidence of linkage to autism
Authors: Bradford Yuki , Haines Jonathan , Hutcheson Holli , Gardiner Marybeth , Braun Terry , Sheffield Val , Cassavant Tom , Huang Wen , Wang Kai , Vieland Veronica , Folstein Susan , Santangelo Susan , Piven Joseph
Published: August 2002

We investigated the effect of incorporating information about proband and parental structural language phenotypes into linkage analyses in the two regions for which we found the highest signals in our first‐stage affected sibling pair genome screen: chromosomes 13q and 7q. We were particularly interested in following up on our chromosome 7q finding in light of two prior reports of linkage of this region to developmental language disorder, since one of the diagnostic criteria for autism is absent or abnormal language development. We hypothesized that if the language phenotype were genetically relevant to linkage at the chromosome 7q locus, then incorporating parents phenotypes would increase the signal at that locus, and most of the signal would originate from the subset of families in which both probands had severe language delay. The results support these hypotheses. The linkage signals we obtained on chromosome 7q as well as at least one signal on chromosome 13q are mainly attributable to the subgroup of families in which both probands had language delay. This became apparent only when the parents’ history of language‐related difficulties was also incorporated into the analyses. Although based on our data, we were not able to distinguish between epistasis or heterogeneity models, we tentatively concluded that there may be more than one autism susceptibility locus related to language development. © 2001 Wiley‐Liss, Inc.
Human metabotropic glutamate receptor 2 gene (GRM2): Chromosomal sublocalization (3p21.1–p21.2) and genomic organization
Authors: Martí Sylvia Bort , Cichon Sven , Propping Peter , Nöthen Markus
Published: August 2002

Imbalances in glutamatergic function have been implicated in the pathogenesis of neuropsychiatric disorders. Consequently, glutamate receptors genes are promising candidates in search of susceptibility genes for these disorders. In the present study, we report the chromosomal sublocalization and genomic organization of the human metabotropic glutamate receptor 2 gene (GRM2). Using monochromosomal hybrid cell lines of NIGMS Mapping Panel 2 (Coriell Cell Repository), the GRM2 gene was localized to human chromosome 3, confirming previously reported localization. In addition, using the radiation hybrid panel RH3 (Research Genetics), we sublocalized the GRM2 gene to chromosomal region 3p21.1–p21.2. The genomic organization of the GRM2 gene was established using a premade library of adaptor‐ligated, human‐specific genomic DNA fragments. The gene consists of 5 exons, with sizes ranging from 74 to 1,076 bp. © 2001 Wiley‐Liss, Inc.
Comparison of chorionic gonadotropin expression in human and macaque (Macaca fascicularis) trophoblasts
Authors: Wilken Jason A. , Matsumoto Kikuko , Laughlin Lisa S. , Lasley Bill L. , Bedows Elliott
Published: August 2002

We have designed novel DNA primers that allow us to detect the expression of the subunits of chorionic gonadotropin (CG) from a variety of species of the order Primates. Using these primers, reverse transcriptase‐polymerase chain reaction (RT‐PCR), and standard cloning techniques, we detected the expression of a single gene for the common glycoprotein hormone (GPH) α‐subunit and at least two genes for the CG β‐subunit in trophoblasts of Macaca fascicularis (cynomolgous macaque (cm)) at gestational day (GD) = 26 (± 2d). No cmCG expression was detected at GD = 35–40. When sequences of cmGPH‐α and cmCG‐β genes were compared to the corresponding genes of other primates, we found that the α‐subunit of M. fascicularis was highly conserved compared to other primate species. However, cmCG β‐subunits appeared to be less conserved, residing between those of human CG‐β and baboon CG‐β when analyzed phylogenetically. Of particular interest was a three amino acid stretch in one of the expressed cmCG‐β genes that is distinct from all other primates studied. Our findings imply that not only does the expression of multiple CG β‐subunit genes appear to be common to Old World monkeys, but that the presented methodology will greatly facilitate our ability to understand primate evolution. Am. J. Primatol. 56:89–97, 2002. © 2002 Wiley‐Liss, Inc.