Pacemaker failure resulting from radiation damage

The authors present a case of radiation-induced pacemaker failure. After 2,000 rad (20 Gy) of photon irradiation for metastatic bronchogenic carcinoma, the pulse generator circuitry failed, producing a "runaway" rhythm. This suggests that present pacemaker circuitry may be more susceptible to irradiation than previously believed, and that even modest radiation doses can induce life-threatening arrhythmias.     

Studies on the mechanism of synthesis and release of the procoagulant activity from leukaemic cells

The synthesis and release of procoagulant activity (PCA) from leukaemic leucocytes was studied in anin vitro culture system stimulated by endotoxin. Puromycin, actinomycin-D, vinblastine, colchicine, dibutyryl cyclic AMP and ouabaln were added to the culture system to study some of the metabolic processes of these cells in relation to synthesis and release of PCA. It was found that production of PCA is an active process and depends on new protein synthesis. The release of PCA from cells can be inhibited by vinblastine, an inhibitor of microfilament and microtubules in the cell. The optimal release of PCA occurs at pH 7.2-@#@ 7.4 at 37°C and is not inhibited by the ATPase inhibitor ouabaln. Dibutyryl cyclic AMP inhibits the release/synthesis of PCA. Gram negative septicaemia and endotoxinaemia are capable of increased production and release of PCA from leukaemic cells and could contribute to the coagulation fallure seen in this disease.     

Primary angiitis of CNS : neuropathological study of three autopsied cases with brief review of literature

Primary angiitis of CNS(PACNS) or granulomatous angiitis of CNS is a rare inflammatory disease of small blood vessels mostly confined to the CNS. The clinical and pathological features of 3 autopsied cases are described. Clinically all the three PACNS patients were young males, age ranging from 19 to 31 years. All presented with varied neurological manifestations. There was no evidence of systemic disease in any of the cases. The ESR was normal and CSF analysis showed chronic meningitic pattern. The cerebral angiogram in one case was normal and the CT scan done in another case showed multiple intracerebral haematoma due to vasculitis. Brain biopsy was not done. Diagnosis was made at post-mortem examination. Histology showed characteristic but variable degree of granulomatous and non-granulomatous angiitis of small vessels. Venulitis with parenchymal haemorrhages was the predominant feature and in one case phlebitis with thrombosis was noted. Since the disease responds to steroids and immunosuppressive therapy, establishing antemortem diagnosis is important. In view of the association of angiitis of CNS with bacteria and viral infections, their role in the evolution of the disease needs to be investigated.     

Endocrine effects of dehydroepiandrosterone and its fluorinated analog,fluasterone, in rats

Cancer chemoprevention is the use of pharmacologic agents to inhibit the development of cancer. The adrenal steroid dehydroepiandrosterone (DHEA) has demonstrated chemopreventive efficacy in animal models of tumorigenesis. However, due to DHEA's undesirable hormonal actions, the fluorinated analog fluasterone (fl‐DHEA), which also has chemopreventive characteristics, was synthesized as a potential alternate agent. It is not known whether fl‐DHEA has hormonal actions. The endocrinologic effects of DHEA and fl‐DHEA in adult male and female Fischer 344 rats were examined following 28 days of daily oral treatment. Initial doses tested were 30 and 300 mg/kg/day for each drug (n=12/sex/group), which are equivalent to 104 and 1,042 µmoles/kg/day DHEA, and 103 and 1,034 µmoles/kg/day fl‐DHEA. However, due to weight loss at the high dose, doses were lowered to 150 mg/kg/day for each drug (521 and 517 µmoles/kg/day DHEA and fl‐DHEA, respectively). Administration of DHEA resulted in dose‐dependent increases in plasma DHEA and DHEA‐S 1 h after dosing in week 4. DHEA produced an estrogenic effect in female rats expressed as decreased plasma FSH and LH, inhibition of ovulation, prolonged estrus, and increased uterine estrogen receptors. DHEA also increased plasma levels of androstenedione in males and females. Administration of fl‐DHEA increased the estrus cycle length due to a prolonged diestrus II phase and decreased the weights of the uterus, prostate, seminal vesicles, and testes. In addition, fl‐DHEA decreased plasma FSH, LH, and tissue estradiol, and increased plasma dihydrotestosterone levels in both sexes. These results indicate that fl‐DHEA is hormonally active and additional studies are warranted to further describe its endocrinologic effects. Drug Dev. Res. 58:169–178, 2003. © 2003 Wiley‐Liss, Inc.     

Balanitis xerotica obliterans – a review

Balanitis xerotica obliterans (BXO) is a scarcely known disease, wrongly considered rare. With a high degree of suspicion and histologic examination, the condition will prove to be much more frequent than one generally believes. The etiology of the condition is unknown at present. Many cases of BXO occurring after circumcision may be cases of secondary phimosis due to BXO not being recognized at the time of surgery. Most of the cases of BXO are seen in the third to fifth decades of life, even though they may occur at the extremes of age. Biopsy of the lesions is not essential in all cases and is indicated to differentiate from penile cancer and in atypical cases. Early diagnosis and treatment of BXO are very important in preventing the urological complications of the diseases such as urethral stricture. Treatment of BXO depends on the anatomic location of the lesions and their extent and severity, together with the rapidity of progression of the disease process. The treatment may vary from topical corticosteroids, laser vaporization in early cases to meatoplasty and urethroplasty in extensive cases. Topical pharmacotherapy is useful in the early stages to reduce the initial symptoms and slow down the progression, but is not effective in all cases and is not the curative treatment of disease. Meatal stenosis, phimosis, scar adhesions, fissures, erosions of glans and prepuce and involvement of the urethra are indications for surgical treatment. Surgery seems to be the only treatment that can relieve the symptoms of advanced disease. Modified circumcision, with total removal of inner preputial layer, definitively relieves phimosis without any recurrence. Meatotomy will not prevent the recurrence of meatal stenosis. Excision of the scleroatrophic tract and grafting of the glans base, coronal sulcus, and the end of the shaft give a complete relief of pain during erection and intercourse in circumcised patients with balanopreputial adhesions and restore the elasticity of the skin of penile shaft. These procedures have been shown to yield excellent functional results during a follow-up period of up to 4 years. BXO involving anterior urethra can be treated by 2-stage urethroplasty or substitution urethroplasty. The complete excision of the stricture and flap urethroplasty seems to be better than a 2-stage procedure. However, at the present time, it is not possible to say that surgery can completely resolve this chronic and progressive disease. Despite many reports in the literature of cases of BXO associated with squamous cell carcinoma, the etiologic relationship between the two conditions is uncertain.     

Development of a new metastatic human breast carcinoma xenograft line.

Xenografts originated from human tumours offer the most appropriate research material for in vivo experimental research. However, primary human breast carcinomas are difficult to grow when transplanted in athymic mice: tumour take is less than 15%. Recently, we have achieved 60% tumour take by injecting tumour cell suspensions mixed with Matrigel. Human breast xenografts originated from primary breast carcinoma also frequently show the potential to metastasize spontaneously. In the present study, we generated a human breast carcinoma xenograft line (UISO-BCA-NMT-18) that shows 100% tumorigenicity and 80-100% lung metastasis when transplanted s.c. in athymic mice. We have studied in detail the characteristics of the xenograft and the patient''s tumour from which the xenograft line originated. Both the xenograft and the patient''s tumour showed intense staining for mutant p53 nuclear protein, and high expression of U-PA, PAI and u-PAR. In vivo growth of the xenograft is stimulated by exogenous supplementation of oestrogen. This xenograft is continuously growing in mice and has shown 80-100% metastasis for the last three successive in vivo passages. This well-characterized, oestrogen-responsive, metastatic breast carcinoma xenograft line will provide excellent research material for metastasis-related research.     

Daily CT localization for correcting portal errors in the treatment of prostate cancer

Introduction: Improved prostate localization techniques should allow the reduction of margins around the target to facilitate dose escalation in high-risk patients while minimizing the risk of normal tissue morbidity. A daily CT simulation technique is presented to assess setup variations in portal placement and organ motion for the treatment of localized prostate cancer.

Methods and Materials: Six patients who consented to this study underwent supine position CT simulation with an alpha cradle cast, intravenous contrast, and urethrogram. Patients received 46 Gy to the initial Planning Treatment Volume (PTV₁) in a four-field conformal technique that included the prostate, seminal vesicles, and lymph nodes as the Gross Tumor Volume (GTV₁). The prostate or prostate and seminal vesicles (GTV₂) then received 56 Gy to PTV₂. All doses were delivered in 2-Gy fractions.

After 5 weeks of treatment (50 Gy), a second CT simulation was performed. The alpha cradle was secured to a specially designed rigid sliding board. The prostate was contoured and a new isocenter was generated with appropriate surface markers. Prostate-only treatment portals for the final conedown (GTV₃) were created with a 0.25-cm margin from the GTV to PTV. On each subsequent treatment day, the patient was placed in his cast on the sliding board for a repeat CT simulation. The daily isocenter was recalculated in the anterior/posterior (A/P) and lateral dimension and compared to the 50-Gy CT simulation isocenter. Couch and surface marker shifts were calculated to produce portal alignment. To maintain proper positioning, the patients were transferred to a stretcher while on the sliding board in the cast and transported to the treatment room where they were then transferred to the treatment couch. The patients were then treated to the corrected isocenter. Portal films and electronic portal images were obtained for each field.

Results: Utilizing CT–CT image registration (fusion) of the daily and 50-Gy baseline CT scans, the isocenter changes were quantified to reflect the contribution of positional (surface marker shifts) error and absolute prostate motion relative to the bony pelvis. The maximum daily A/P shift was 7.3 mm. Motion was less than 5 mm in the remaining patients and the overall mean magnitude change was 2.9 mm. The overall variability was quantified by a pooled standard deviation of 1.7 mm. The maximum lateral shifts were less than 3 mm for all patients. With careful attention to patient positioning, maximal portal placement error was reduced to 3 mm.

Conclusion: In our experience, prostate motion after 50 Gy was significantly less than previously reported. This may reflect early physiologic changes due to radiation, which restrict prostate motion. This observation is being tested in a separate study. Intrapatient and overall population variance was minimal. With daily isocenter correction of setup and organ motion errors by CT imaging, PTV margins can be significantly reduced or eliminated. We believe this will facilitate further dose escalation in high-risk patients with minimal risk of increased morbidity. This technique may also be beneficial in low-risk patients by sparing more normal surrounding tissue.     

Classifying choledochal cysts using hepatobiliary scintigraphy

PURPOSE: This retrospective study was designed to classify choledochal cysts on the basis of the findings of hepatobiliary scintigraphy. METHODS: Twenty-one patients with choledochal cysts (15 female, 6 male; mean age, 20 years) proved on the findings of endoscopic retrograde cholangiopancreatography (ERCP) or surgery and histopathologic analysis were included in the study. Two nuclear medicine physicians, blinded with regard to cholangiographic and operative details, were asked to review and to classify the type of choledochal cyst seen on the hepatobiliary scan. Later, scintigraphic results were compared with ERCP and surgical findings for a reference standard. RESULTS: The findings of hepatobiliary scintigraphy correlated with ERCP and surgical findings in 18 of 21 cases (86%). Scintiscans correctly identified all type 1 cysts (12/12). The sensitivity of scintigraphy in diagnosing type 4 cysts was 66% (6 of 9 cases). It underestimated the intrahepatic extent of disease in type 4a biliary cysts (37%). CONCLUSION: This study illustrates the utility of hepatobiliary scintigraphy in diagnosing type 1 and 4 choledochal cysts.