תוצאת חיפוש

In Vitro Interferon-Gamma Release in Diagnosis of Cutaneous Adverse Drug Reactions

S. Halevy, A. D. Cohen, N. Grossman

Dermatology Dept, Skin Bank and Investigative Dermatology Laboratory, Soroka University Medical Center and Faculty of Health Sciences; Ben-Gurion University of the Negev, Beer Sheba

Diagnosis of cutaneous adverse drug reactions is an accepted terminology. Is a challenge. Drug-specific T-cell clones (CD4+ or CD8+), with a Th1- or a Th2-type cytokine-release pattern, may be generated from the peripheral blood in CADRs. In vitro drug-induced cytokine-release suggests a drug-specific immune response, and may implicate the drug as a possible inducer of the skin reaction.

We evaluated the diagnostic role of in vitro drug-induced interferon-gamma (IFN-γ) release from peripheral blood lymphocytes in patients with CADRs. We studied 22 patients with CADRs following intake of 45 drugs (1-4 drugs per patient). Drugs were classified into 3 categories of suspicion. 17 patients who took 39 drugs of the same type (1-4 drugs per patient) without developing adverse reactions, served as controls. In vitro drug-induced release of IFN-γ from peripheral blood lymphocytes, following in vitro challenge with the unmodified drugs, was evaluated.

The mean IFN-γ increase following 45 drug tests (60.8±85.2%) was higher (p<0.05) than in controls after 39 drug tests (30.1±27.7%). Significance was greater (p<0.005) when the mean IFN-γ increase for the 24 highly suspected drugs (75.1±93.4%) and that for the controls were compared.

This study suggests that the in vitro drug-induced IFN-γ release test may serve as a diagnostic tool in CADRs.

Tuberculous Meningitis in HIV

R. Elazary, Y. Kalish

Medical Dept., Hadassah University Hospital, Ein Karem, Jerusalem

The increase in prevalence of tuberculous meningitis during the past decade has been attributed in part to the increase of AIDS. Failure to diagnose HIV can cause irreversible damage and even death. We describe a man with AIDS admitted through the emergency room because of high fever and headaches for more than a month, He was cachectic and had nuchal rigidity without major neurological deficit. Brain imaging was normal and lumbar puncture showed neutrophils, lymphocytes, hypochloremia, elevated protein, and decreased glucose; cryptococcal antigen was negative but acid-fast staining was positive.

Anti-TB chemotherapy was started using 4 drugs and dexamethasone was also given. Considerable improvement in his general condition followed rapidly.

Use of corticosteroids in tuberculous meningitis has been a major issue. They are added to antimicrobial agents in order to decrease reactivity of inflammatory mediators and thus reduce central nervous system damage.

We review several controlled studies in which steroids were added to treat tuberculous meningitis. The conclusions of most were that they decrease morbidity and mortality, especially of those moderately to severely ill. Most considered as ungrounded the possibility of exacerbating latent tuberculous, or any other opportunistic infection outside the central nervous system. However, it is currently recommended to add prednisone, 1 mg/kg/d for 2-4 weeks when initiating antituberculous treatment.
 

Diagnostic Laparoscopy for Abdominal Lymphoma

D. Lev-Chelouche, D. Margal, J.M. Klausner, A. Szold

Dept. of Surgery B, Tel Aviv-Sourasky Medical Center (Affiliated with Sackler Medical Faculty, Tel Aviv University)

Imaging-guided (CT/US) percutaneous biopsy has significantly improved diagnosis of intra-abdominal lymphoma. However, in many cases the tissue retrieved may be inadequate for specialized studies such as immunophenotyping or cytogenetic analysis that may be required for a complete analysis of lymphoma or determination of therapy.

The success of diagnostic laparoscopy in the diagnosis and staging of gastrointestinal malignancies suggests that it could be used for intra-abdominal lymphomas as well. We describe our experience in 15 patients with suspected lymphoma who underwent diagnostic laparoscopy during 1995-98.

Preoperative investigation performed in all included percutaneous FNA in 9 without conclusive diagnosis. Laparoscopy was diagnostic for lymphoma in 14 (93%) while in 1 there was a false negative result due to sampling error and the lymphoma was only diagnosed at a second laparoscopy.

There was no mortality nor any major complication. Average hospital stay was 2 days and patients were then referred for further oncological treatment. Our experience shows that diagnostic laparoscopy is a safe and efficient tool and without major complications in diagnosing abdominal lymphoma.
 

Newer Diagnostic and Therapeutic Methods in Lung Cancer

R. Rubinstein, R. Breuer, R. Chisin

Dept. of Medical Biophysics and Nuclear Medicine, and Institute of Pulmonology, Hadassah University Hospital, Ein Karem, Jerusalem

Positron emission tomography (PET), when used with F-18 fluoro-deoxyglucose (FDG), contributes to the evaluation of patients with lung cancer. This technique of imaging detects active tumor tissue by showing increased radiopharmaceutical uptake by metabolically active cells.

Thus, PET assists in the early diagnosis of pulmonary malignancies that appear only as non-specific findings on CT-scan or chest X-ray. In addition, it is helpful in staging lung cancer before and after resection, chemotherapy or radiotherapy, or their combined use.

We performed 135 FDG-PET studies between July '97-April '99. and present our preliminary results with examples of the main indications for PET in lung cancer.
 

Screening for Early Detection of Prostatic Cancer

A. Neheman, Y. Shotland, Y. Metz, A. Stein

Dept. of Urology, Carmel Hospital, Lady Davis Medical Center, Haifa

Prostatic cancer (PC) is second only to lung cancer as a cause of cancer mortality in men word-wide. In Israel it is the most common cause of cancer mortality in men, after lung cancer and colo-rectal cancer.

We screened, for the first time in Israel, for prostatic cancer using serum levels of PSA and a digital rectal examination (DRE). The purpose was not only to diagnose PC but also to increase public awareness of the condition.

300 men in the Haifa area who met statistical criteria for early diagnosis of PC participated. They filled a questionnaire regarding risk factors for PC (age, family history (FH) of prostatic and breast cancer, cigarette smoking, alcohol consumption, previous PSA sampling) and were examined. Those who had out-of-ragne, age-related PSA values, or a pathologic DRE underwent trans-rectal ultrasound (TRUS) examination and guided biopsy of the prostate. Those with a positive biopsy for PC underwent radical prostatectomy or radiation therapy.

41 (14.3%) had out-of-range, age-related PSA levels and 10 (3.5%) had a pathologic DRE. 39 (13.3%) underwent TRUS and biopsy and 6 (2.04%) had clinically significant PC, all early stages (Gleason 4-6).

Correlation between age and PSA has been proven statistically significant (p<0.05). Symptoms of urinary tract obstruction and nocturia were related to a high PSA (p=0.035 and 0.002, respectively). Those with PC had at least 1 symptom of urinary tract obstruction; 6 (15.3%) who underwent TRUS and biopsy and a FH of prostate cancer. However, no subject with a FH of PC had biopsy-proven cancer. Those with PC had PSA values from 4.9 to 31.8 ng/ml (9.6 median). Age-related PSA had a positive predictive value of 17.1%.

Results of our annual screening for early detection of PC using age-related PSA, and DRE are encouraging: cases detected were clinically significant and treatable. It would appear that screening for PC will result in decreasing the incidence of metastatic cancer and therefore mortality. 
 

Diagnosis and Therapy in Acute Stroke: A Rehabilitation Center Viewpoint

M. Motin, J. Streifler, A. Tsur, H. Ring

Neurological Rehabilitation Dept., Loewenstein Rehabilitation Center, Ra'anana; Neurological Unit, Rabin Medical Center, Golda Campus, Petah Tikva and Sackler School of Medicine, Tel Aviv University, Ramat Aviv

The extent of the diagnostic work-up of patients with acute stroke was evaluated in 101 patients admitted for rehabilitation during a 4-month period in 1997. This included specific blood tests and neuro- and cardiac imaging, and compared the extent of work-up in a community hospital versus a rehabilitation center. Comparisons were also made with similar investigations 10 and 20 years earlier.

Results demonstrated that the trend to admit younger stroke patients (<50 years) to neurological (as opposed to medical) departments observed between 1977-1987 persisted in 1997.

The use of CT scan increased dramatically from 1977 to 1987 (19% vs 78%), and in 1997 was actually 100% The use of carotid duplex and echocardiography increased steadily during the 3 decades reaching 26% and 28% respectively. Tests for thrombophilia were seldom done. However, in neurological departments it was done in about 50% of the younger stroke patients. In neurology departments carotid duplex was done 2 to 3 times more often than in medical departments.

During rehabilitation imaging tests were done once or more in almost half the patients. The results and those of additional blood tests, have led to modification of antithrombotic treatment in 14% of the younger group and 4% of the older group.

We have clearly shown that while stroke work-up has become more comprehensive in recent years, there is still much to do in this field. Stroke units or teams in our general hospitals will increase stroke awareness, improve work-up and hasten definitive treatment.
 

A Molecular Method of Diagnosis of Congenital Adrenal Hyperplasia

Shoshana Israel, Chaim Brautbar

Tissue Typing Unit, Hadassah Medical Center, Jerusalem

Congenital adrenal hyperplasia (CAH) is caused mainly by deficiency of the 21-hydroxylase enzyme. The disease may appear in the classical salt-losing, simple virilizing forms or as a mild, nonclassical form. 21-hydroxylase is encoded by the CYP21B gene on the short arm of chromosome 6, in the midst of the human leukocyte antigen (HLA) complex, between HLA Class I and Class II regions.

We describe a method for identifying mutations in the CYP21B gene. It is based on amplification of the gene using the polymerase chain reaction and identification of mutations with sequence-specific oligo-probes. The mutations identified were: V281 and P30L responsible for nonclassical CAH, and I2 splice, Q318X, I172N, cluster E6, and a deletion including 8bP in the third exon (8bP del) responsible for the classical form of CAH.

We also analyzed 2 families affected with the classical form of CAH which demonstrate possible complications in genotyping. Typing for HLA haplotypes can be helpful in certain cases, as demonstrated in 1 of the families presented. In this case it was necessary to distinguish between 2 possible genotypes: 1 with the mutations in tandem on 1 chromosome and the other with the mutated genes on both chromosomes. HLA haplotyping enabled the assignment of the mutations to the relevant chromosomes and thus allowed correct genetic counseling.

The other family demonstrated the importance of CYP21B genotyping in individuals with the nonclassical form of CAH. This form may consist of 1 mild and 1 severe mutation, representing a serious potential for transmitting the classical form of CAH.

Treatment of Phenyl-Ketonuria due to Dihydropteridinereductase Deficiency 

B. Sela, J. Blonder, I. Peled, G. Schwartz

Institute for Pathological Chemistry and Child Development, Sheba Medical Center, Tel Hashomer; Clinical Biochemistry Dept., Sackler Faculty of Medicine, Tel Aviv University

Most cases of hyper-phenylalaninemia are due to deficiency of phenyl-alanine hydroxylase that converts phenyl-alanine to tyrosine. This enzymic reaction is facilitated by the co-factor tetrahydrobiopterin (BH₄). A defect in the latter substrate leads to increased phenyl-alanine in 1-2 cases per million live births. Such cases are characterized by a degenerative brain process, and pronounced neurologic symptoms that cannot be prevented by a low phenyl-alanine diet alone.

In 3 male newborns a deficiency of dihydropteridine reductase (DHPR) activity was diagnosed, the last in a sequence of 3 enzymes involved in the formation of BH₄. Successful outcome of treatment as well as the results of failure to diagnose and treat affected newborns are described, with emphasis on the logistic problems involved in mass screening.

Giant Lesions in Multiple Sclerosis: A Diagnostic Challenge 

Bruria Shalmon, Dvora Nass, Zvi Ram, Anat Achiron

Institute of Pathology, Neurosurgery Dept. and Neuroimmunology Unit, Sheba Medical Center, Tel Hashomer

Multiple sclerosis is the most common demyelinating disease of the central nervous system affecting young adults, in which destruction of the axon myelin sheath disturbs signal transduction. The disease course is usually remitting and relapsing, but sometimes there is steady neurological deterioration.

The diagnosis depends mainly on an adequate clinical history and neurological examination. Evoked potentials, elevated cerebrospinal fluid gamma globulin with oligoclonal bands, and imaging studies, mainly magnetic resonance imaging (MRI), also contribute to the diagnosis.

Multiple sclerosis may occasionally present as a mass lesion that clinically and radiologically is indistinguishable from a brain tumor. We present 2 cases of giant tumefactive lesions, proven by brain biopsy to be of demyelinating nature.

Infectious Mononucleosis in Adults - A Diagnostic Challenge

G. Goltzman, S. Nagornov, M. Horwitz, M.J. Rapoport

Dept. of Internal Medicine C, Assaf Harofeh Medical Center, Zerifin

The adult form of mononucleosis caused by Ebstein-Barr virus (EBV) is different from the disease in children and adolescents. In most adults there is no pharyngitis or lymphadenopathy, fever is much more prolonged, abnormal liver function is frequent and lymphocytosis and the presence of atypical lymphocytes are not common. Such an atypical disease presentation often results in delayed diagnosis and unnecessary treatments. We describe 2 adults with such atypical presentations and complications of EBV infection.

Prioritizing Suspected Diagnosis of Both Brain and Abdominalinjuries: Is it a Problem?

Leon Levi, Moshe Michaelson

Dept. of Neurosurgery and Trauma Unit, Rambam Medical Center, Haifa

Current guidelines for management of suspected head and abdominal injuries are based on retrospective studies like that of Wisner & al, Following a recent review in this journal by Y. Kluger & al, which was based on non-Israeli data, we decided to define the current status at our trauma center.

We compare our data of 18 months of hospital admissions for acute trauma in which head CTs were done with those of 5 articles advocating specific protocols for decisions in pre-laparotomy diagnosis.

In the 861 cumulated cases, compared with the 800 of Wisner & al, craniotomy was required in 15% vs 7% (p<0.05); laparotomy was much less frequent, 2.7% vs 12.9% (p<0.05). The chance of finding a case requiring both craniotomy and laparotomy was 1 in 300.

As the clinical condition of multiple trauma involving the head and abdomen is becoming less frequent and includes diverse situations, a comprehensive algorithm might be inaccurate. Good clinical judgment of the clinician and teamwork are therefor preferable.

Microlaparoscopy in Diagnostic and Operative Gynecologic Procedures 

Dov Dicker, Shmuel Nitke, Itai Bar-Hava, Raul Orvieto, Zion Ben-Rafael, Arie Dekel

Depts. of Obstetrics and Gynecology, Rabin Medical Center, Beilinson and Golda Campuses, Petah Tikva; and Sackler School of Medicine, Tel Aviv University

A recent further development in laparoscopic surgery is microlaparoscoopy. The technique is identical to standard 10 mm laparoscopy except for the use of small, 2 mm scopes and trocars. We used this technique in 19 patients treated from June 1998 to February 1999.

The advantages of microlaparoscopy are: smaller incisions, less risk of damage to pelvic organs and less postoperative pain. However, the use of microlaparoscopy for operative procedures is limited to simple operations due to the limited field of vision. We urge our colleagues to consider microlaparoscopy whenever diagnostic laparoscopy is needed.

Cost-Effectiveness of Imaging Procedures in Knee Injuries 

Moshe Leshno, Hagai Amir, Dalia Leshno

School of Business Administration, Hebrew University of Jerusalem; Dept. of Orthopedics, Tel Aviv Medical Center; Israel Defense Forces, and Faculty of Management, Tel Aviv University

It is clear to experts in the health care industry that with regard to medical decision-making, considering costs of medical devices is not a good index, but it is highly important to include medical aspects. This approach guarantees an advance and an appropriate method.

We present a cost-effectiveness analysis to target the optimal strategy of how to use medical diagnostic devices in cases of knee injuries. Today, one of the more common medical emergency referrals seen worldwide is in the area of orthopedics, knee injuries in particular. They can harm soft tissue, bone tissue, or both simultaneously. The diagnosis of soft tissue injury is difficult at best. Among the devices helping the clinician make an accurate diagnosis are MRI and ultrasound (US).

We conclude that US is superior to MRI in this condition. This is especially true when the orthopedic examination leads to the suggestion of arthroscopy. The results were not modified, and a sensitive study of the parameters that influence the decision- making process was undertaken. Decision-makers should not consider medical outcome alone, but should take into account the costs. A clinical study should validate the assumption on which this study was based.

Evaluation of Laparoscopy and Laparoscopic Ultrasound in Pancreatic Lesions

P. Schachter, Y. Avni, A. Rosen, A. Czerniak

Depts. of Surgery A and of Gastroenterology, Wolfson Medical Center, Holon

Pancreatic lesions present a diagnostic challenge. Even modern imaging techniques are not sensitive enough in determining resectability of pancreatic tumors. A substantial proportion of patients therefore undergo unnecessary surgical exploration. We determined the impact of laparoscopy and laparoscopic ultrasound (LAPUS) examinations on surgical decision-making in 60 patients with pancreatic lesions.

Of 48 with solid pancreatic lesions, 22 were defined by LAPUS as having nonresectable tumors, while conventional imaging studies defined only 9 of them as such. 3 of these 9 underwent successful resections of the pancreatic mass. Surgical intervention was ruled out by LAPUS in 16 patients (33.3%) but 26 had resectable lesions of whom 25 underwent surgery. 3 of this group were found to have nonresectable tumors at surgery, a false-positive rate of 6.2%. Overall sensitivity of LAPUS in our series was 88%.

In 12 patients with cystic pancreatic lesions LAPUS contributed significantly to the preoperative decision due to clear imaging of the cystic lesion. Additional information was obtained from ultrasound guided-biopsy of the cyst wall, as well as determination of tumor-marker levels in the cystic fluid aspirate. LAPUS contributed significantly to operative management in 58%.

Multilocular Cystic Mass of the Kidney: A Diagnostic Challenge

Judy Kleinmann, Simon Negelev

Urology Dept., Assaf Harofeh Medical Center, Zerifin

Multilocular cystic masses of the kidney present a diagnostic challenge because they may be malignant. Renal cell carcinoma with multilocular cysts has been reported. We present 4 cases in which the preoperative differential diagnosis was between a benign and a malignant multilocular cystic kidney mass.

Our results, combined with those of 33 previously reported cases, reveal that only 32% of cases were diagnosed correctly preoperatively. In 21% of these patients the preoperative clinical evaluation did not correctly diagnose malignancy: 24% of them yielded false negative and 21% false positive results. Angiography was more accurate than CT, US or aspiration of cysts. Frozen section was inaccurate in 55% of cases.

There is no reliable diagnostic test to distinguish between a malignant and a benign multilocular cystic mass. Invasive angiography is more accurate than other modalities. A therapeutic decision has to be made between nephron-sparing and radical surgery in each case. When nephron-sparing surgery is considered, the possible need to perform radical nephrectomy in second-look surgery must be taken into account.