Five years experience of predictive testing for myotonic dystrophy using linked DNA markers.

We report on a 5 year experience in providing presymptomatic and prenatal molecular diagnostic services for myotonic dystrophy, using closely linked markers, representing 235 completed results in 161 families. Only 10 analyses (4.3%) proved uninformative, but a further 5 requests (1.9%) could not be reported because of uncertainty in clinical status. Seven of 81 (8.6%) patients considered to be at low risk on clinical grounds were found to be at high risk of carrying the gene. The importance of interpreting molecular results in conjunction with clinical findings is emphasised by the illustrative examples provided. Careful clinical examination and appropriate investigation remain a cornerstone of diagnosis in myotonic dystrophy and are crucial if errors in assigning genotype status by molecular means are to be minimised.

Localisation of the myotonic dystrophy locus to 19q13.2-19q13.3 and its relationship to twelve polymorphic loci on 19q.

The order of fourteen polymorphic markers localised to the long arm of human chromosome 19 has been established by multipoint mapping in a set of 40 CEPH (Centre d'Etude de Polymorphisme Humain, Paris) reference families. We report here the linkage relationship of the myotonic dystrophy (DM) locus to twelve of these markers as studied in 45 families with DM. The resulting genetic map is supported by the localisation of the DNA markers in a panel of somatic cell hybrids. Ten of the twelve markers have been shown to be proximal to the DM gene and two, PRKCG and D19S22, distal but at distances of approximately 25 cM and 15 cM, respectively. The closest proximal markers are APOC2 (apolipoprotein C-II) and CKM (creatine kinase, muscle) approximately 3 cM and 2 cM from the DM gene respectively, in the order APOC2-CKM-DM. The distance between APOC2, CKM and DM (of the order of 2 million base pairs) and their known orientation should permit directional chromosome walking and jumping. The data presented here should enable us to determine whether or not new markers are distal to APOC2/CKM and thus potentially flank the DM gene.

Changes in quantitative SPECT thallium-201 results associated with the use of energy-weighted acquisition.

The effect of utilizing energy-weighted acquisition on quantitative analysis of SPECT thallium-201 images was evaluated by simultaneously acquiring energy-weighted and windowed projection images in ten patients. The paired image sets were processed identically and evaluated by probability analysis of defect magnitude as indicated by a commercially available software analysis package. It was predicted that defect magnitude would increase as a result of improved image contrast. This was confirmed experimentally. One should be cautious in relying on strict quantitative criteria in cardiac studies with thallium-201, especially when major changes in the imaging system or technique are introduced.

Arterial oxygen desaturation during ambulatory colonoscopy: predictability, incidence, and clinical insignificance.

Arterial hemoglobin oxygen saturation was prospectively monitored in 103 consecutive patients undergoing office colonoscopy to determine the incidence of any clinical characteristics which might predict arterial desaturation to less than 90%. Baseline saturations were obtained prior to premedications and continuously during the examination using a finger mounted pulse oximeter. Intravenous premedication regimens varied from none to a maximal dose of 50 mg of meperidine and 10 mg of diazepam. All colonoscopies included cecal intubation and were performed by one investigator employing a video colonoscope. The incidence of desaturation was 41% without significant variation among the sedation groups. Age was positively correlated with desaturation (p less than 0.05). Sex, obesity, history of lung or heart disease, chronic cardiac medications, and baseline saturation percentage failed to be sensitive predictors of desaturation. No parameter could be correlated with prolongation of desaturation below 90%. No adverse outcomes or complications were noted during the periendoscopy period, suggesting that oximetry monitoring during outpatient colonoscopy may not be clinically useful.

Presymptomatic detection and prenatal diagnosis for myotonic dystrophy by means of linked DNA markers.

The close genetic linkage between the loci for apolipoprotein CII (ApoCII) and myotonic dystrophy makes presymptomatic detection and prenatal diagnosis feasible. We report three years' service experience of providing presymptomatic detection and prenatal diagnosis for myotonic dystrophy in 99 families. Careful clinical study of older family members remains important. The introduction of new probes (CKMM and BCL4) has helped to solve the problem of uninformativeness owing to unhelpful genotype distribution in a family. Nevertheless, informativeness cannot be guaranteed and families should be studied before pregnancy is undertaken whenever possible. Presymptomatic testing and prenatal diagnosis for myotonic dystrophy are soundly based. All affected subjects should have DNA banked for future use when other family members may require genotype information.

A simplified method for the routine determination of effective renal plasma flow.

Quantitative renal data (i.e., glomerular filtration rate or effective renal plasma flow) often would be useful ancillary information when radionuclide renography is carried out. The added time, and therefore cost, of obtaining quantitative information might be the main reason a department does not routinely perform a quantitative study, although there is no added radiation or risk to the patient. To simplify the procedure for determining effective renal plasma flow with I-123 orthoiodohippurate (OIH), the published methodology was modified to eliminate the repetitive preparation of a standard solution. This allows the routine incision of effective renal plasma flow (ERPF) determination in I-123 OIH renography with minimal impact on departmental operations.

Concepts in computed tomography of the thorax.

A number of concepts in the CT evaluation of the thorax have been reviewed. The concepts have been presented through anatomic images generated on a specific CT system, but any equivalent system could have produced similar images. The important conclusions derived as a result of this review are: 1. Slice thickness, volume averaging and volume sampling are interrelated. Slice thickness and the orientation and inherent subject contrast of the anatomy to be studied usually determine the quality of the image obtained. 2. Thin section imaging (i.e., 5 mm and especially 1.5 mm) can demonstrate thoracic anatomy rarely (if ever) observed on thicker images (i.e., 10 mm). Although impractical for general analysis, thin section imaging provides insight into the potential limitations of a standard approach to thoracic evaluation. 3. CT analysis of the normal anatomy of the pericardium is incomplete. Although pathology related to the pericardium has been presented in the literature, more work is required to define: 1, the relationship, on CT, of the pericardium to structures within its confines; 2, abnormalities within the mediastinum that may affect the pericardium, and 3, lesions in the lung that may invade the mediastinum and pericardium. 4. The excellent contrast sensitivity of CT (aided by iodine infusion or bolus injection techniques and dynamic scanning) does not suffice to resolve certain problems in thoracic analysis. Extrapleural signs, the concept of invasion versus abutment, and the discrimination of benign from malignant mediastinal nodes continue to present diagnostic dilemmas in CT analysis of the thorax. 5. Interesting cases provide models for demonstrating CT pitfalls, mimics, and rarities. CT can be a valuable tool in resolving diagnostic dilemmas in some cases but creates dilemmas in others. 6. CT reformation images of the thorax can be dynamically generated on the scanner console. This hands-on technique can be a valuable tool for teaching anatomy in resident training programs.

Appearance of hyperostosis frontalis interna on indium-111 leukocyte scans: potential diagnostic pitfall.

The appearance of hyperostosis frontalis interna on an [111In]leukocyte scan is reported. Recognition of the potential for normal accumulation of 111In-labeled white blood cells within this common process involving the skull is necessary to avoid misdiagnosis.

Hemobilia associated with hepatic artery aneurysms: scintigraphic detection with technetium-99m-labeled red blood cells.

Biliary tract bleeding is an unusual cause of upper gastrointestinal hemorrhage. Rupture of hepatic artery aneurysms is one of the least common etiologies of hemobilia. Both cholescintigraphy and [99mTc]red blood cell scintigraphy are useful in the diagnosis of this rare disorder. The combination of focal obstruction on cholescintigraphy and intermittent visualization of the major bile ducts on red blood cell scintigraphy should suggest the diagnosis of hemobilia and prompt an angiogram to determine the cause.

Hemobilia. An unusual cause of segmental bile duct obstruction.

Hemobilia is reported as an unusual cause of segmental bile duct obstruction. The finding of focal "hot spots" caused by delayed washout of the tracer from the obstructed segments is discussed. Whenever the clinical triad of pain, intermittent jaundice, and gastrointestinal bleeding is associated with the above findings, the diagnosis of hemobilia should be entertained.

Thyroid uptake and imaging with iodine-123 at 4-5 hours: replacement of the 24-hour iodine-131 standard.

A study was carried out to determine the suitability of utilizing a 4 to 5 hr interval from administration of iodine-123 to imaging and uptake measurement as a replacement for the 24-hr standard originally established with iodine-131. In 55 patients who underwent scintigraphy at 4 and 24 hr, there was no discrepancy between paired images. In 55 patients who had uptake measured at 4 and 24 hr and in 191 patients who had uptake measured at 5 and 24 hr, the early measurements proved equal or better discriminants of euthyroid from hyperthyroid patients. In our institutions, these findings and the logistical advantages of completing the exam in 4-5 hr led us to abandon the 24-hr study in the majority of patients.

Bone scintigraphy in the diagnosis of mastoiditis.

Bone scintigraphy has proven utility in the early diagnosis of osteomyelitis, but the authors were unable to find any report of its specific application to mastoiditis. Three cases of mastoiditis are presented in which the bone scan findings predicted the histopathologic findings.