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.

Hospitalization for Renal Colic: Epidemiological Features and Clinical Manifestations

Yahav Oron, Amir Shahar, Eran Dolev

Sheba Medical Center, Tel Hashomer; Israel Defense Forces Medical Center; Meir General Hospital, Sapir Medical Center, Kfar Saba; and Dept. of Medicine H, Sourasky-Tel Aviv Medical Center

The medical records of all patients referred to the emergency department (ED) of Sheba Medical Center for renal colic during 1996 were analyzed. Patients discharged from the ED and those hospitalized were compared.

There was no significant difference between the 2 groups with regard to average age or sex distribution. Statistically significant differences were found with regard to frequency of chills and fever, history of renal colic, referral for renal colic during that year or hospitalization for renal colic or nephrolithiasis, previous positive imaging, stone removal by surgery or extracorporeal shock wave lithotripsy, fever exceeding 37.5^o and administration of fluids, pethidine or pramin in the ED, prolonged stay in the ED and previous appendectomy.

A conditional regression model tested the predictive value of each of those factors. Inclusion of independent variables into the model led to an overall correct classification rate of 84.43%, with 44.83% sensitivity and 93.16% specificity. There were correlations between referrals for renal colic, overall renal colic rate and average monthly temperature, so there was no pure correlation between average monthly temperature and referrals to the ED for renal colic.

The major indications for hospitalization were actually the clinical ones, indicating either an active metabolic disease or suspected obstruction of the urinary tract. Treatment in the ED and duration of the visit indicated disease severity.

Family Physicians' Attitudes to Clinical Guidelines for Treatment of Diabetes 

Sasson Nakar, Shlomo Vinker, Tal Baro-Aloni, Eliezer Kitai

Dept. of Family Medicine, Rabin Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Clinical guidelines are systematically developed statements designed to help practitioners and patients make decisions about appropriate health care for specific clinical states. Attitudes of family physicians to clinical guidelines for treating diabetes and guidelines in general were evaluated from anonymous questionnaires answered by physicians participating in continuous medical education throughout the country (May-June 1998). The questionnaire dealt with attitudes to the recently published specific guidelines for treating the diabetic patient and overall perception of the efficacy of clinical guidelines.

293 family physicians, aged 40.2‏7.0 responded (83%). 93.5% appreciated the guidelines and thought them applicable. Most (83.7%) reported the guidelines to be of help in their daily work; 31.4% said they were oversimplified; a quarter said they aimed main at containing costs. Most respondents preferred written guidelines of up to 5 pages.

In view of our results, attention can now be turned to developing ways to implement the guidelines. To improve adherence, they need to be short and the rate of publication of new clinical guidelines should be slowed.

Early Detection of Glaucoma by a Mobile Unit

S. Kurtz, M. Goldenfeld, S. Melamed

Sam Rothberg Glaucoma Center, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer

Glaucoma, the third leading cause of blindness in the western world, is characterized by painless, gradual loss of visual fields which may lead to severe visual impairment or even blindness. In 4 years of operation of a mobile glaucoma unit for screening and early diagnosis of glaucoma, 10,037 subjects aged 18-95 years were screened (4504 women, 45%); 55% were under 50 years (Graph 1).

Ocular hypertension was diagnosed in 8.0%; primary open angle glaucoma (POAG) in 0.8%, with 2/3 already under treatment, the rest newly diagnosed. Pseudo-exfoliative glaucoma was diagnosed in 0.2%; only 2 cases had closed angle glaucoma; 91% of those screened were normal (Fig. 4; age stratification, Graph 3).

POAG increased with age, from 0.2% in those under 40 years to 10% in those over 80; POAG was more common in men, but OHT was similar in both sexes (6.0% vs. 5.3%). There was no correlation between incidence of POAG and place of work except in the Sorek Nuclear Center (1.9% vs. 0.8%, p=0.11). Other conditions significantly more frequent in POAG than normals were diabetes mellitus (x 2.5), systemic hypertension (x 4), myopia (x 2) and history of intraocular surgery (x 6).

Congenital Syphilis: Need for Adequate Antenatal Care

Mark Friedberg

Pediatrics B Dept., Soroka Medical Center, Beer Sheba

Congenital syphilis is well-known and treatable with penicillin. Diagnosis in the neonate and young child may be difficult and consequently morbidity and mortality can be high. Prevention in children is of utmost importance and can be achieved by proper antenatal care and adequate follow-up of pregnant women. This includes identification of pregnant women at risk for contracting syphilis. The case presented demonstrates this need.

Measuring Residual Urine by Portable Ultrasound Scanner

Santiago Richter, Rachel Hag'ag, Moshe Shalev, Israel Nissenkorn

Urology Dept. and Outpatient Clinic, Meir Hospital, Kfar Saba and Sackler Faculty of Medicine, Tel Aviv University

Urethral catheterization, the standard method of measuring residual urine, is uncomfortable and associated with risk of infection and trauma to the urethra. It has also been reported as inaccurate to a certain extent. We compared catheterization with ultrasound scanning in a prospective study of 52 men and 3 women.

100 measurements of postvoiding residual urine by portable ultrasound scanner, were each followed immediately by urethral catheterization (both procedures performed by an experienced nurse in our outpatient clinic). A difference of >25€ml between measurements by scanner and by catheter was considered significant.

The range of residual urine measured by scanner was 1-425 ml, and by catheter 1-410 ml. There was good matching between the 2 methods in 85 of 100 measurements (scanning accuracy 85%). In 30/85 matching was excellent while in 55 cases the mean difference was 8.5±6.2 ml, range 1-24 ml. The accuracy of scanning was 85%; there was perfect matching between the 2 methods in 30 cases. In the remaining 15 cases the mean difference was 41.8±13.6 (range 25-56).

Each catheterization took 4-5 minutes and scanning 30 seconds. There were no complications after catheterization, but all reported discomfort and dysuria for 1-2 hours thereafter. Scanning was absolutely uneventful in all.

The cost per catheterization, including medication, disposable materials and personnel time was approximately 80 NIS. Our 80-90 measurements of residual urine a month require annually about 80 hours and a budget of about NIS 80,000. Scanning requires only 8 hours, while the cost of the portable scanner is significantly less than NIS 80,000 and it can be used for more than a year.

We conclude that measuring urine residual with the noninvasive scanner instead of by catheterization is easier, more accurate, and more cost-effective.

Interactive Effects of Perinatal Co-Infection with Hepatitis B and HIV Viruses

Galia Soen-Grisaru, Asher Barzilai

Pediatric Infectious Disease Unit, Chaim Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

We report the case study of a 1-year-old girl who was perinatally infected with both hepatitis B (HBV) and HIV viruses. The clinical presentation and treatment are described. We examined the interaction between the 2 viruses and the possible effects of the interaction on the development of each virus and on treatment. Our findings demonstrate that combined HIV and HBV infections intensified deterioration, as the HBV liver disease aggravated the HIV infection. The medication of choice was Lamivudine, since it prevents the transcription of both viruses.

Orthostatic Hypotension as a Manifestation of Malignant Lymphoproliferative Disease

H. Semo, A. Adunsky, E. Grossman

Depts. of Geriatric Medicine and of Medicine D, Chaim Sheba Medical Center, Tel Hashomer

An 85-year-old man was admitted with 6-month history of incapacitating orthostatic hypotension. Investigation led to the discovery of sympathetic dysautonomia, sensorimotneuropathy and malignant lymphoproliferative disease. Several attempts to treat the orhypotension or the neoplastic disease failed to improve his condition. Orthostatic hypotension precipitated by sympathetic dysautonomia may be an infrequent effect of early malignant lymphoproliferative disease.

Experience with Under-Water Birth

Eylon Lachman, Zvi Finelt

Dept. of Obstetrics and Gynecology, Yoseftal Hospital, Eilat

Underwater birth is now deemed an acceptable type of delivery. Safety is a recurring consideration, the main concern being that of drowning. But in reports of 19,000 underwater births no untoward events were noted. Also, need for pain relief and of intervention during labor were both reduced. The short term indicators of neonatal outcome were good. A recent review explains 5 different physiological factors which inhibit initiation of fetal breathing under warm water. Many studies have shown no increase in risk of infection of either mother or baby. We report our experience with 26 women, 23 of whom actually delivered in the pool with excellent results. We believe that birth under water is safe and beneficial if done properly for low-risk patients.

Are Testes in Oligo/Azoospermia Homogenous or Heterogenous?

David B. Weiss, Shoshana Gottschalk-Sabag, Elchanan Bar-On, Zvi Zukerman

Kupat Cholim Meuhedet, Jerusalem; Male Infertility and Cytology Units, Shaare Zedek Medical Center, Jerusalem; and Andrology Unit, Rabin (Beilinson) Medical Center, Petah Tikva

We determined whether a single testicular specimen is sufficient to represent qualitatively the spermatogenic process within the testes of azoospermic or severely oligospermic infertile men. In 191 testes of azoospermic patients and in 26 of those with severe oligospermia, fine needle aspirations at 3 different sites of each testis were performed. Aspirated material from each puncture was stained and in each smear all spermatogenic cells, as well as Sertoli cells, were identified. Testes were classified according to the most mature spermatogenic cell type present, or the presence of only Sertoli cells. The homogeneity of the testicular spermatogenic process was then evaluated. There was an overall intratesticular difference between aspirates in 14.1% of azoospermic testes and in 26.9% of severely oligospermic testes with regard to the most mature spermatogenic cell type. When spermatozoa were the most mature cell type, they were detected in all of the 3 aspirates in 71.4% of the testes. In 18.4% or 10.2% of this group of testes they were retrieved in only 1 or 2 of the aspirates, respectively. In testes in which spermatids or spermatocytes were the most mature spermatogenic stage, these cell types were detected in all 3 aspirates in only 36.4% and 68.0%, respectively. In azoospermic patients with full testicular spermatogenesis, the likelihood of retrieving spermatozoa from the testes was 84.3%, 92.7% and 100% in 1, 2 and 3 specimens, respectively. The following conclusions were drawn: There is a wide range of testicular heterogeneity in azoospermia or very severe oligospermia for diagnosing the testicular spermatogenic pattern. In azoospermia, specimens from several testicular sites are required. It is strongly recommended that no assisted fertilization be offered to azoospermic patients unless prior evaluation of the spermatogenic pattern in the seminiferous tubules is determined.

Central Cord Syndrome in the Elderly Who Fall: a Diagnostic Trap

A. Adunsky, H. Semo, S. Levenkrohn

Geriatric Rehabilitation Dept., Chaim Sheba Medical Center, Tel Hashomer

Acute post-traumatic spinal injury is common and usually poses no diagnostic difficulties. Following a low-energy fall, the onset of acute central cord syndrome in the elderly is not common and is frequently misdiagnosed. Men aged 60 and 81, and a woman aged 75 are described, in whom central cord syndrome was overlooked. Awareness of this condition is important to avoid incorrect diagnosis and hazardous management.

Macroenzymes: an Interesting Laboratory Finding, without Clinical Relevance

C. Perry, H. Peretz, E. Graf, O. Ben-Tal, A. Eldor

Hematology Dept. and Biochemistry Laboratory, Tel Aviv-Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University

Macroenzymes are complexes of serum enzymes with proteins which have a higher molecular weight and longer plasma half-life than the normal enzyme. The presence of macroenzymes is suggested by finding increased serum enzyme activity, not associated with symptoms. Thus, macroenzymes can cause diagnostic errors and the performance of unnecessary tests or invasive procedures. We describe 2 patients with highly elevated serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK) due to formation of complexes with immunoglobulin G. 1 patient had LDH of 4500 u/L but was otherwise normal and in the second CK was elevated with no evidence of ischemic heart disease. Awareness of the phenomenon of macroenzymes may save the patient long and sometimes invasive investigation.

Participation of Patients with Uret-Eral Calculi in Clinical Decision Making, and Level of Anxiety

Ilana Margalith, Amos Shapiro

Hadassah-Hebrew University School of Nursing, and Dept. of Urology, Hadassah Medical Center, Jerusalem

In a study examining the relationship between patient participation in clinical decision making and levels of anxiety, patients were offered a choice of treatment for ureteral calculus. 42 received information about 2 treatment options, ultrasound fragmentation of the stone through a ureteroscope and extracorporeal shock wave lithotripsy (ESWL), and were asked to choose the method that they preferred. 54 received treatment decided on by the physician without their participation in the decision making process. Anxiety was measured before meeting with the physician, immediately after the meeting and on hospitalization for treatment. The contribution of the patient's perception of participation in the decision- making process and level of education was also examined. There was a decrease in level of anxiety after meeting with the physician only among those who did not actually participate in the decision-making process (p<0.05). There was no change in the level of anxiety among those offered choice of treatment. However, a decrease in anxiety was evident among patients who perceived that they had received information about their illness and its treatment (p<0.01). This was not the case for patients who perceived themselves as participants in decision making unless they had a relatively high-level of education (p=0.05).

Separation of Conjoined Twins: The Anesthesiologist's Perspective

Zvi Grunwald, Yacov Katz

Dept. of Anesthesiology, Rabin Medical Center, Beilinson Campus and Schneider Children's Hospital, Petah Tikva

Managing anesthesia care for separation of conjoined twins poses a special challenge for the anesthesia team. Early preparation, thorough understanding of the anatomical and the physiological consequences of this complex anomaly, as well as careful coordination with the teams of surgeons, nurses and operating room personnel are mandatory to assure successful separation of the conjoined twins. It is recommended that the mother be transferred to and the babies be delivered at a tertiary care medical center, like the Children's Hospital. Special attention is devoted during the surgical procedure to cardiovascular stability, drug disposition, fluid balance and temperature control. The multidisciplinary team approach makes this complex surgery a success. When postoperative survival cannot be guaranteed for both twins, close contact and consultation is mandated with the parents, medical personnel and religious and legal advisors.