Israel Medical Association Journal

 Background: Hemorrhagic radiation cystitis (HRC) is a significant clinical problem that occurs after pelvic radiation therapy and is often refractory.

Objectives: To evaluate the efficacy and safety of hyperbaric oxygen therapy (HBO) for HRC.

Methods: Daily 90 minute sessions of HBO at 2 ATM 100% oxygen were given to 32 HRC patients with American Society of Therapeutic Radiology and Oncology (ASTRO) grades 3-4 hematuria.

Results: The median age was 72.5 (48–88 years). The median time interval between radiation therapy and HBO was 4 years (1–26 years). The patients received a median of 30 HBO sessions (3–53). Hematuria resolved in 27 patients (84%) and persisted in 5. Cystectomy was required in two, and ileal-conduit and bilateral percutaneous nephrostomies were performed in one and two patients, respectively. With a median follow-up of 12 months (5–74 months), the hematuria cleared completely in 16 patients (59%) and mild hematuria requiring no further treatment recurred in 10 others. Another patient with ASTRO grade 4 hematuria needed bladder irrigation and blood transfusions. Complications included eardrum perforation in four patients and transient vertigo and mild hemoptysis in one case each. None of them required HBO discontinuation.

Conclusions: HBO controlled bleeding in 84% of the patients. A durable freedom from significant hematuria was achieved in 96% of the patients. HBO seems to be an effective and safe modality in patients with HRC.

Objectives: To assess opioid use during a 6 year period (2001–2006) among cancer patients served by Clalit Health Services, the largest health management organization in Israel.

Methods: Purchasing data of opioids authorized for use in Israel were obtained from the computerized databases of Clalit for the period 2001–2006. Patients' demographic and cancer morbidity data were extracted. The data were analyzed by translating the purchased opioids (fentanyl patch, oxycodone, buprenorphine, methadone, hydromorphone) to oral morphine equivalents (OME).

Results: During the study period 182,066 Clalit members were diagnosed with cancer; 58,443 (32.1%) of them died and 31,628 (17.3%) purchased opioids at least once. In 2001, 7.5% of Clalit cancer patients purchased opioids at least once within 5 years of the initial diagnosis. Between 2002 and 2006 this percentage increased consistently, reaching 9.9% in 2006. The average daily dose of opioids increased from 104.1 mg OME in the year 2001 to 115.2 mg OME in 2006 (11% increase). The average duration of opioid purchasing was 5.0 ± 8.3 months (range 1–84 months, median 2). During the study period 19,426 cancer patients who purchased opioids at least once died; only 14.3% (3274) were still alive 2 years after their first opioid prescription.

Conclusions: Opioid purchasing increased during the study period, especially during the final months of life. Children (0–18 years old) and elderly male patients (≥ 65 years) began opioid treatment later compared to other age groups. Only a few patients had an opioid early enough to relieve their pain. 

Objectives: To assess the ability of perfusion-weighted imaging to differentiate between high grade gliomas and brain metastases.

Methods: During 5 months, 21 patients (age 40–85, median age 61, 16 males and 5 females) with either glioblastoma multiforme (GBM) or metastasis (pathology proven), underwent MRI for assessment of the tumor prior to surgery. Most of the scans were done at 3 Tesla. The scans included perfusion-weighted imaging sequences. Perfusion in the tumor, in the peritumoral edema and in normal tissue were assessed using Functool® software. The ratios of tumor perfusion and peritumoral edema perfusion to normal tissue perfusion were calculated and compared.

Results: Bleeding artifact precluded perfusion assessment in four patients. There was no statistically significant difference between the tumor perfusion ratios of high grade gliomas and those of metastases. The edema perfusion ratios were higher in GBM than in metastases (P = 0.007).

Conclusions: Perfusion-weighted imaging of peritumoral edema can help to differentiate between GBM and metastases.

Objectives: To investigate the reasons for non-adherence associated with cardiovascular risk factors among Bedouins.

Methods: We identified Bedouin patients with HTN, DM or LMD from medical records and randomly selected 443 high adherent and 403 low adherent patients. Using trained interviewers we conducted in-depth structured interviews regarding knowledge and attitudes to chronic illness and its treatment, health services evaluation, and socio-demographic factors.

Results: The study population included 99 high and 101 low adherent patients. More low adherent patients agreed that traditional therapy can replace prescribed medications for DM, HTN or LMD (47% vs. 26%, P < 0.01), and 10% used only traditional medications. Also, more low adherent patients believed that the side effects of prescribed drugs are actually worse than the disease itself (65% vs. 47%, P < 0.05), and 47% cited this as a reason for discontinuing drug treatment (47% vs. 31%, P < 0.05).

Conclusions: Our findings suggest that in this minority population the basis for non-adherence derives directly from patients' perceptions of chronic disease and drug treatment. A focused intervention should emphasize the importance of early evidence-based drug therapy with open patient-physician dialogue on the meaning of chronic disease and the side effects of prescribed drugs.

Objectives: To retrospectively determine the clinical response to ¹³¹I-MIBG therapy at low doses in patients with refractory neuroblastoma.

Methods: We performed a retrospective chart review of 10 patients with neuroblastoma treated with ¹³¹I-MIBG at Rambam Health Care Campus from 1994 to 2012. Clinical data, number of ¹³¹I-MIBG courses delivered, toxicities, and clinical responses were reviewed. MIBG scan was performed after each course.

Results: Twenty-one courses of ¹³¹I-MIBG were delivered to 10 patients (3 girls, 7 boys). Their mean age was 3.8 years (range 1.5–6 years). All patients received several protocols of chemotherapy including the high dose form. Three patients received three courses of ¹³¹I-MIBG with a minimum of 6 weeks between each course, five patients received two courses, and two patients received only one course. An objective response to the first course was obtained in nine patients and to the second course in six of eight, and in three children who underwent the third course the pain decreased. One patient has no evidence of disease, four are alive with disease, and five died of the disease. No unanticipated toxicities were observed.

Conclusions: Low dose ¹³¹I-MIBG is an effective and relatively non-toxic treatment in neuroblastoma disease palliation. Rapid and reproducible pain relief with ¹³¹I-MIBG was obtained in most of the children. Treatment with systemic radiotherapy in the form of low dose ¹³¹I-MIBG was easy to perform and effective in cases of disseminated neuroblastoma, demonstrating that this primary therapy can be used for palliative purposes.

Scientific journals are ethically bound to cite Professor Dr. Carl Clauberg's Nazi medical crimes against humanity whenever the eponym Clauberg is used. Modern articles still publish the eponym citing only the rabbit bioassay used in developing progesterone agonists or antagonists for birth control. Clauberg’s Nazi career is traced to his having subjected thousands of Jewish women at the Ravensbruck and Auschwitz-Birkenau death camps to cruel, murderous sterilization experiments that are enthusiastically described by incriminating letters (reproduced here) between him and the notorious Nazi Reichsführer-SS Heinrich Himmler. The experiments were carried out in women’s Block 10 in Auschwitz-Birkenau where Clauberg’s colleague Dr. Josef Mengele worked alongside. After Germany lost World War II in 1945 Mengele fled to South America, where he lived to an old age. Clauberg was caught by Russian soldiers, put on trial in the Soviet Union for his crimes against humanity, and imprisoned in 1948. In 1955 he was repatriated to Germany, once again imprisoned for his crimes, and belatedly expelled from the German Medical Association. To estimate the contemporary usage of the names Mengele and Clauberg, Internet hits were recorded for Clauberg C or Mengele J (with and without adding the term Auschwitz) with the Google and Scirus search engines. The ratios of hits for combinations of these terms reveal that relative to Mengele, Clauberg’s name is barely known. We propose that journals and books printing the eponym Clauberg cite its derivation and reference to the convicted Nazi criminal. The present article can serve for such citations.

Background: Multidrug-resistant tuberculosis (MDR-TB) presents a difficult therapeutic problem due to the failure of medical treatment. Pulmonary resection is an important adjunctive therapy for selected patients with MDR-TB.

Objectives: To assess the efficacy of pulmonary resection in the management of MDR-TB patients.

Methods: We retrospectively reviewed the charts of MDR-TB patients referred for major pulmonary resections to the departments of thoracic surgery at Assaf Harofeh and Wolfson Medical Centers. For the period under study, 13 years (from 1998 to 2011), we analyzed patients’ medical history, bacteriological, medical and surgical data, morbidity, mortality, and short-term and long-term outcome.

Results: We identified 19 pulmonary resections (8 pneumonectomies, 4 lobectomies, 1 segmentectomy, 6 wedge resections) from among 17 patients, mostly men, with a mean age of 32.9 years (range 18–61 years). Postoperative complications developed in six patients (35.3%) (broncho-pleural fistula in one, empyema in two, prolonged air leak in two, and acute renal failure in one). Only one patient (5.8%) died during the early postoperative period, three (17.6%) in the late postoperative period, and one within 2 years after the resection. Of 12 survivors, 9 were cured, 2 are still under medical treatment, and 1 is lost from follow-up because of poor compliance.

Conclusions: Pulmonary resection for MDR-TB patients is an effective adjunctive treatment with acceptable morbidity and mortality.
 

Background: Determining the prognosis of patients with heart failure is essential for patient management and clinical trial conduct. The relative value of traditional prognostic criteria remains unclear and the assessment of long-term prognosis for individual patients is problematic.

Objectives: To determine the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of patients with idiopathic dilated cardiomyopathy.

Methods: We investigated the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of individual patients in a large, representative, contemporary cohort of idiopathic dilated cardiomyopathy (IDCM) patients referred to Johns Hopkins from 1997 to 2004 for evaluation of cardiomyopathy. In all patients a baseline history was taken, and physical examination, laboratory studies, echocardiogram, right heart catheterization and endomyocardial biopsy were performed.

Results: In 171 IDCM patients followed for a median 3.5 years, there were 50 long-term event-free survivors (LTS) (median survival 6.4 years) and 34 patients died or underwent ventricular assist device placement or transplantation within 5 years (NLTS; non-long-term survivors) (median time to event 1.83 years. Established risk factors (gender, race, presence of diabetes, serum creatinine, sodium) and the use of accepted heart failure medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers) were similar between the two groups. Although LTS had younger age, higher ejection fraction (EF) and lower New York Heart Association (NYHA) class at presentation, the positive predictive value of an EF< 25% was 64% (95% CI 41%–79%) and of NYHA class > 2 was 53% (95% CI 36–69%). A logistic model incorporating these three variables incorrectly classified 29% of patients.

Conclusions: IDCM exhibits a highly variable natural history and standard clinical predictors have limited ability to classify IDCM patients into broad prognostic categories. These findings suggest that there are important host-environmental factors still unappreciated in the biology of IDCM.
 

The role of carbon in the development of life and as the structural backbone of all organisms is universally accepted and an essential part of evolution. However, the molecular basis is largely unknown and the interactions of carbon with nitrogen and oxygen in space are enigmatic. In 1985, the previously unknown form of carbon, coined fullerene, was discovered. We hypothesize that by virtue of the unique properties of fullerene, this hollow, ultra-robust, large, purely carbon molecule was the earliest progenitor of life. It acted as a stable universal biologic template on which small molecules spontaneously assembled and then formed, by further assembly, a surface mantle (here termed rosasome) of larger molecules. We submit that this process, by its inherent flexibility, initiated evolution, allowing the emergence of parallel diverse rosasome lines responding selectively to varying spatial environments. For example, rosasomal lines mantled with nucleotide and peptide layers are conceived as primordial forerunners of the ubiquitous ribosome. Moreover, the parallel independent and interdependent evolution of rosasome lines would be more rapid than sequential development, refute precedence of either DNA or RNA, and explain the evolution of integration of two subunits with different structures and functions in ribosomes and of the triplet nature of the codon. Based on recent astronomical data, this hypothesis supports the concept that life is not a singularity. This concept also suggests a potential vehicle for therapeutics, biotechnology and genetic engineering.