M L Manco-Johnson

Diagnosis of autosomal dominant polycystic kidney disease in utero and in the young infant.

Autosomal dominant polycystic kidney disease (ADPKD), once thought to be a disease of the adult, is now being reported with increasing frequency in childhood. We report five cases and review eight cases from the literature of ADPKD diagnosed in the fetus or the young infant by sonographic evaluation and a positive family history. Renal enlargement (85%) was the most common and most helpful sonographic finding. Approximately 50% of the patients already had cysts large enough to detect by ultrasound. Increased renal echogenicity was present in nine of 10 cases. Although every case in this review had one parent affected with ADPKD, only five of 13 (38%) were aware of their disease prior to their pregnancy. Renal cystic disease diagnosed in the fetus and young infant should trigger an investigation of the family history and sonographic screening.

Optimizing factor prophylaxis for the haemophilia population: where do we stand?

Summary.  The hallmark of severe haemophilia, defined as a circulating level of factor (F) VIII (haemophilia A cases) or FIX (haemophilia B cases) of < 1%, is recurrent bleeding into muscles and joints (haemarthroses) from an early age of life. The inevitable result of such bleeding is progressive joint damage, leading to disabling arthritis that is typically evident within the first 2 decades of life in people with haemophilia who have limited or no access to regular factor replacement therapy, or those in whom factor replacement therapy is ineffective because of the presence of high‐titre inhibitors. For children with severe haemophilia and no evidence of inhibitors, the unwanted musculoskeletal complications of severe haemophilia can be effectively prevented by the early initiation of a programme of long‐term factor prophylaxis. In order to achieve the best outcome (a perfect musculoskeletal status for age) the programme of prophylaxis should be started before the onset of joint damage (primary prophylaxis). The gold standard primary prophylaxis regimen (the Malmö protocol) was pioneered and tested in Sweden and involves the infusion of 20–40 IU of FVIII per kg body weight on alternate days (minimum three times per week) for haemophilia A cases, and 20–40 IU kg−1 of FIX twice weekly for haemophilia B cases. This protocol is, however, demanding on peripheral veins and very expensive. Modifications of the parent protocol such as starting primary prophylaxis with once‐weekly infusions via peripheral veins with rapid escalation to full‐dose prophylaxis or dose escalation based on frequency of bleeding are increasingly implemented in haemophilia treatment centres in countries that can afford the high cost of such programmes. These modified programmes can be achieved in the majority of young children with severe haemophilia without the need for central venous access devices (e.g. Port‐a‐Caths) and with avoidance of device‐associated complications such as infection and thrombosis. In at least one centre, experience with arteriovenous fistulae as a strategy to ensure reliable venous access is being accumulated. The issues of compliance (adherence) to recommended prophylaxis protocols and when, if ever, to stop a programme of primary prophylaxis once started are real and require ongoing prospective studies. Such studies should incorporate outcome measures such as health‐related quality‐of‐life and economic analyses.

Combined thrombolytic and anticoagulant therapy for venous thrombosis in children.

OBJECTIVES To evaluate safety, efficacy, and outcome after combination thrombolytic and anticoagulant therapy. STUDY DESIGN An open nonrandomized clinical protocol with prospective standardized monitoring and data collection. Children with a documented first episode of deep vein thrombosis were treated with urokinase 4400 U/kg load and per hour with unfractionated heparin at 10 U/kg/h. At 48 hours heparin infusions were increased to achieve a therapeutic level for 5 days. Children were given therapeutic warfarin for at least 3 months. Outcome was assessed at 48 hours and > or =1 year with history, physical examination, high-resolution imaging, and Doppler ultrasonography +/- impedance and photo plethysmography. RESULTS Thirty-two children were treated. There was 1 thrombotic death, 1 nonfatal thrombus progression, and 1 pulmonary embolism. At 48 hours half of the children showed substantial clot lysis, and on follow-up these children had complete resolution and had no symptoms. Three children with poor early clot lysis had recurrent thromboemboli, pulmonary embolism, or both, 2 had limb pain and swelling, and 2 had asymptomatic swelling. Two children had minor bleeding, whereas systemic reactions were common. CONCLUSIONS Combination therapy in children (urokinase and unfractionated heparin) was safe and efficacious. A prospective, randomized, controlled study in children is needed.

Tracheoesophageal fistula in utero. Twenty-two cases.

A retrospective review of 22 infants born with tracheoesophageal fistula (TEF) with in utero sonograms was performed and the literature was reviewed. TEF or esophageal atresia should be considered when there is polyhydramnios and an absent fluid‐filled stomach; these findings were seen in 32% of our cases. Amniotic fluid flows freely through some TEFs, resulting in a normal amount of amniotic fluid and a fluid filled stomach (six of 22 patients), while in other cases, the fluid does not traverse the fistula easily and polyhydramnios results. Polyhydramnios was present in 62% of our cases and was the most common sonographic finding. The earliest age at which polyhydramnios was diagnosed was 24 weeks. Sonography will detect approximately one third of fetuses with TEF; an improved outcome is expected in these fetuses.

Posterior urethral obstruction. Prenatal sonographic findings and clinical outcome in fourteen cases

Fourteen cases of fetal urethral obstruction were reviewed retrospectively. The purpose of this study was to emphasize the following: 1) prenatal sonographic findings: 2) clinical outcome: and 3) associated congenital anomalies. Decreased amniotic fluid volume complicated 12 pregnancies (86%). A dilated posterior urethra was identified in nine fetuses (64%) and an enlarged bladder in 13 (93%). Evaluation of the fetal kidneys revealed hydronephrosis in 81%, increased parenchymal echogenicity in 73% and macroscopic renal cysts in 15%. There were seven live births, but only two neonates survived beyond 5 weeks. Pulmonary hypoplasia contributed to the five postnatal deaths. Associated congenital anomalies were noted at autopsy in six cases.

Fetal lateral ventricular ratio determination during the second trimester.

Ventriculomegaly may be diagnosed sonographically by identifying abnormal ventricular size. The lateral ventricular ratio (LVR) is a useful index in differentiating normal‐sized ventricles from ventriculomegaly. The purpose of this study was to validate previously reported data establishing the normal range for LVR during the second trimester. Prior to 24 weeks, the diagnosis of ventriculomegaly may be difficult since the LVR normal range is quite large. The LVRs for 122 normal fetal ultrasound examinations were calculated based on measurements obtained by three observers. Data were obtained for fetuses during each week of gestation from 15 to 25 weeks. Lateral ventricular ratios varied from 56 +/‐ 18 per cent (mean +/‐ 2 standard deviations) at 15 weeks to 33 +/‐ 4 per cent at 25 weeks. The lateral ventricular width (LVW) range for normal fetuses was 0.7 to 1.1 cm as compared with a LVW range of 1.1 to 2.7 cm for 16 fetuses with hydrocephalus diagnosed during the second trimester. In conclusion, the LVR is extremely useful in differentiating ventriculomegaly from normal ventricular size. Serial ultrasound examinations are often mandatory in the second trimester in order to definitely identify ventriculomegaly. In addition, normal ventricular size may be verified with a LVW of less than 1.1 cm.

Frequency of ovarian cysts in patients with autosomal dominant polycystic kidney disease

Extrarenal cysts occur in patients with autosomal dominant polycystic kidney disease (ADPKD) most frequently in the liver. Ovarian cysts have been reported in women with ADPKD, but their frequency has not been determined. Therefore, we analyzed the historical data in our database of 337 women with ADPKD and 199 of their unaffected female family members (NADPKD). In addition, we prospectively studied 25 nonpregnant, premenopausal women with ADPKD and 25 nonpregnant, premenopausal, age-matched control women recruited from the general population to assess the occurrence of ovarian cysts. No women in either the control or ADPKD groups were receiving exogenous estrogen or progesterone. All women underwent sonographic examination using a 5- or 7.5-MHz vaginal probe. A normal ovarian follicle was defined as a fluid-filled structure less than 2 cm in average diameter, and an ovarian cyst as one of 2 cm or greater. From the historical data, 28% of the women with ADPKD gave a history of ovarian cysts compared with 18% of the NADPKD women (P < 0.05). In the prospective study, the mean age of the women with ADPKD was not different from that of the control women (40.9 +/- 1.2 v 39.3 +/- 1.2 years; P = not significant [NS]). There was no difference in frequency of normal follicles found in women with ADPKD or controls (80% v 96%; P = NS), nor was there a difference in the frequency of ovarian cysts found in women with ADPKD or controls (12% v 12%; P = NS). There was no difference in the calculated ovarian volumes between the women with ADPKD and controls (9.9 +/- 2. 5 v 7.2 +/- 1.2 cm3). Among the women with ADPKD, there was no correlation between mean ovarian volume and mean renal volume, nor was there a significant relationship between the occurrence of hepatic cystic disease and ovarian cysts. Therefore, a prospective imaging study suggests that ovarian cysts have no increased frequency in women with ADPKD compared with women in the general population.

Radiographic Appearance of Diffuse Splenic Hemangiomatosis

The evaluation of splenomegaly in a patient with a consumptive coagulopathy included a liver-spleen scan, an abdominal sonogram, and an abdominal computed tomographic scan, which demonstrated an enlarged spleen with a diffuse parenchymal textural abnormality. A diffuse hemangiomatous pattern was present on splenic angiography. A splenectomy was performed and splenic hemangiomatosis was confirmed. The radiographic findings in this rare entity are presented and discussed.

Optimal treatments for patients with bleeding disorders.

Despite the vast number of published papers relating to the treatment of bleeding disorders there are relatively few controlled prospective studies in this ®eld. This means that many therapeutic decisions are made by reference to incomplete scienti®c data. It is clear that the management of bleeding disorders will continue to evolve, not only because of technological developments but also because of the accumulation of new treatment-related research. A 2-day meeting was held in London on January 15±16, 2001. The aim of the meeting was to discuss the current best practice and to identify areas where further research is required to make the most impact on the optimization of treatment regimes for individuals with bleeding disorders. The meeting was chaired by Louis Aledort, MD, and consisted of a small group of invited experts to discuss aspects of haemophilia care. This group presented and discussed data from existing and recent research in an attempt to identify areas of current consensus and areas that warrant future research. The meeting was sponsored by educational grants donated by a number of pharmaceutical companies, who were invited to send observers to the meeting. This paper is a resume of some of the main points presented and discussed during the 2 days.

Night call in U.S. radiology residency programs

RATIONALE AND OBJECTIVES We acquired information about resident call in radiology programs throughout the United States to allow programs to compare themselves with others and to learn of possible alternate approaches to similar clinical and educational needs. METHODS A 30-question survey was mailed to the program directors of all accredited U.S. radiology residency programs. A second mailing was sent to program directors who did not respond within 3 months. The survey addressed questions of the timing of call during residency training, the frequency of call, the nature of the call experience, and the relation to fellow and faculty call. Questions regarding available technical assistance, resident clinical activities postcall, faculty review of oncall studies, and other relevant issues were included. RESULTS One hundred sixty-six of 206 (81%) of the program directors responded. The amount and type of call taken by radiology residents was highly variable in different programs. The mean number of in-house call days per month was 2.9 (SD = 2.6), 3.3 (SD = 2.2), 2.4 (SD = 1.9), and 1.3 (SD = 1.6) for first-, second-, third-, and fourth-year residents, respectively. The nature of technical and fellow/faculty assistance available to the resident was also variable. CONCLUSION Night call in U.S. radiology residency programs is variable but tends to be concentrated in the second year of residency. Fourth-year residents take less call than other residents, especially close to the time of the written and oral board examinations. Although program directors were satisfied with many aspects of their call systems, most indicated at least one major change they would like to make.