Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

Endogenous protein phosphorylation by resting and activated human neutrophils

NADPH oxidase is an enzyme in the plasma membrane of the neutrophil that catalyzes the production of O2-, a species central to the oxygen- dependent killing mechanisms of this cell. The oxidase is dormant in resting cells and is activated upon the addition of a stimulus. Neutrophils of patients with chronic granulomatous disease (CGD) manifest no oxidase activity when stimulated. The possible role of protein phosphorylation in the activation of NADPH oxidase was examined in normal and CGD neutrophils by measuring the incorporation of 32Pi into proteins as determined by gel electrophoresis followed by autoradiography. Resting neutrophils from normal subjects exhibit at least 40 distinct phosphoprotein bands. The level of phosphorylation of these bands was examined after the addition of phorbol myristate acetate (PMA), opsonized zymosan, digitonin, N-formyl-methionyl- phenylalanine (FMLP), or NaF. PMA and opsonized zymosan increased the phosphorylation of a set of 6 protein bands. Digitonin and FMLP consistently caused the phosphorylation of 4 of these protein bands, while NaF failed to induce increased phosphorylation of any protein band. All activators tested caused the dephosphorylation of one specific protein band. The time course of phosphorylation (dephosphorylation) was examined using PMA as the activating agent. Increased phosphorylation of one protein band was evident by 12 sec after the addition of PMA. The most slowly phosphorylated protein band did not slow evidence of change until 5 min after the addition of PMA. Three of the phosphoproteins examined were phosphorylated either earlier than or concomitant with the activation of NADPH oxidase. CGD neutrophils were compared with normal cells for their ability to phosphorylate proteins in response to PMA. The phosphoprotein banding patterns of CGD neutrophils were identical with those of normal neutrophils in both the resting and activated states. The evidence presented shows that the phosphorylation of proteins is a prominent feature of neutrophil metabolism. The striking similarity of phosphorylation changes induced by the various activators tested suggests that protein phosphorylation may play a role in some aspects of neutrophil activation. Evidence was not obtained, however, regarding a link between protein phosphorylation and activation of NADPH oxidase.     

Peptic ulcer and gastric carcinoma: diagnosis with biphasic radiography compared with fiberoptic endoscopy

The diagnostic value of biphasic radiographic examination of the stomach and duodenum was compared with that of fiberoptic endoscopy in a prospective, blinded study of 385 patients with dyspepsia. This investigation was directed at gastric malignancies and peptic ulcers. Methodologically there is no absolute standard for a study of this kind because histologic examination is useful for detection of cancer but inadequate for ulcers. As an alternative, kappa indexes and the sensitivity and specificity, as derived by Hui and Walter, were calculated and compared. For the detection of gastric carcinoma, radiographic and endoscopic findings had almost perfect agreement beyond chance. For gastric ulcers, radiography and endoscopy had substantial agreement, which became perfect if small ulcers (less than 5 mm) were excluded. For duodenal ulcers, radiography had a lower sensitivity than endoscopy; this disagreement disappeared if small ulcers were excluded. Both methods have equal merit; choice of the initial diagnostic procedure will therefore depend on cost, discomfort to the patient, and risk of complications.     

MR imaging of the scrotum: normal anatomy

High-resolution magnetic resonance (MR) imaging with a surface coil was utilized to evaluate the normal scrotum. Scrotal contents, spermatic canal, and inguinal regions were visualized within the same field of view. Differences in signal intensity in the testis, epididymis, tunica albuginea, fluid, fat, and spermatic cord allowed for clear delineation of these structures in detail. The high contrast and spatial resolution of MR imaging, coupled with the wide field of view and absence of ionizing radiation, make MR imaging well suited for evaluation of the scrotum.     

Dorsal lunate tilt (DISI configuration): sign of scaphoid fracture displacement

Excessive dorsiflexion (dorsal tilting) of the lunate on a lateral wrist radiograph can be an important sign of carpal injury. Lunate dorsiflexion is a well-recognized sign of an intercarpal ligamentous injury pattern known as dorsal intercalated segment instability (DISI). It is less well recognized that excessive dorsal tilting of the lunate (DISI configuration) can also be produced by displacement of a scaphoid waist fracture. Since the management and prognosis of displaced scaphoid fractures may be quite different from those for nondisplaced fractures, radiologists can make an important contribution by recognizing dorsal tilting of the lunate and appreciating that it may be an important, indirect sign of scaphoid fracture displacement, which may not be directly visualized with standard wrist radiography. In this setting, computed tomography or complex motion tomography may be helpful for further evaluation of the scaphoid fracture.     

Chromosome 7 long arm deletion in myeloid disorders: a narrow breakpoint region in 7q22 defined by molecular mapping

The involvement of the erythropoietin (EPO), plasminogen activator inhibitor type I (PAI1), and multi-drug resistance (MDR2) genes located in chromosomal region 7q21-22 was studied in patients with myeloid disorders and with or without a chromosome 7 abnormality. Separated blood mononuclear cells and granulocytes from 21 patients were used in restriction fragment length polymorphism (RFLP) studies with gene- specific DNA probes. A marked weakness of one of the allelic bands was observed in granulocyte-derived DNA from heterozygous patients with monosomy 7. In four patients with a partial deletion of chromosome 7 long arm (7q-), marked weakness of an allelic band was observed in granulocyte-derived DNA with PAI1 probe (four heterozygous patients) and MDR2 probe (one heterozygous patient), implying deletion of these genes. In contrast, the EPO gene was not deleted in these patients, as demonstrated by the presence of two allelic bands of equal strength in granulocyte-derived DNA (two patients) or by gene dosage estimation (two patients). Two allelic bands of equal strength were also observed in three heterozygous patients with an arbitrary probe (pKV13) located in 7cen-q21.3. Unexpected hemizygosity or hybridization bands were not observed in any patient. We conclude that PAI1 and MDR2 are located distally of EPO in 7q22, and that none of these genes is commonly rearranged in myeloid disorders. The chromosome 7 long arm deletion breakpoint is located in a relatively narrow segment between the PAI1 and EPO genes in different patients. The deletion may involve a specific site in DNA, since the genetic distance between the PAI1 and EPO genes is only 3 cM.     

Chronic radiographic lung changes in children with vertically transmitted HIV-1 infection

OBJECTIVE: We prospectively studied children with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 to determine the incidence of chronic radiographic lung changes (CRC) and to correlate these changes with clinical assessments. SUBJECTS AND METHODS: Between 1990 and 1997, we scored 3050 chest radiographs using a standardized form. Group I children (n = 201) were HIV-1-infected at enrollment. Group II children (n = 512) were enrolled prenatally or before 28 days postpartum and subsequently subdivided into group IIa (n = 86), children identified as HIV-1-infected; and group IIb (n = 426), those who were HIV-1-uninfected. CRC were defined as parenchymal consolidations or nodular disease lasting 3 months or more or increased bronchovascular markings or reticular densities lasting 6 months or more. Morbidity was assessed by CD4 counts, viral load, the presence of low oxygen saturation, wheezing, tachypnea, crackles, and clubbing. RESULTS: The cumulative incidence of chronic radiographic lung changes in HIV-1-infected children was 32.8% by 4 years old, with increased bronchovascular markings or reticular densities being most common. Chronic changes were associated with lower CD4 cell counts and higher viral loads. Resolution of these chronic changes was associated with decreasing CD4 cell counts but not with lower rates of clinical findings, viral load, or difference in survival. CONCLUSION: With increased survival, CRC are becoming more common. The resolution of these changes may indicate immunologic deterioration rather than clinical improvement.