Israel Medical Association Journal

The addition of methotrexate to treatment protocols in children with acute lymphoblastic leukemia has been found beneficial in preventing central nervous system relapse. However, MTX[1] itself may be associated with neurologic morbidities, the most significant of which is leukoencephalopathy. The present study describes the clinical spectrum of leukoencephalopathy, which ranges from a subclinical disease manifested only radiologically to a progressive, devastating encephalopathy. The interaction of MTX with other components of the treatment protocol is discussed, as is the effect of leucovorin. A summary is presented of the metabolic pathways that may be involved in the development of MTX toxicity. Researchers are still seeking a biochemical marker to aid in the determination of the amount of MTX that may be safely administered.

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Background: The treatment of patients with recurrent ovarian carcinoma after failure of first and second-line chemotherapy is still debated. Chemical agents used for third and fourth-line therapy usually yield poor results with severe toxic side effects.

Objective: To summarize our experience with goserelin in the treatment of patients with recurrent ovarian cancer.

Methods: From September 1996 to June 1999 we administered goserelin, 3.6 mg subcutaneously every 4 weeks, to 15 patients with advanced and recurrent epithelial ovarian cancer (median age 59.0, median performance status 3.0).

Results: Seven of 15 eligible patients relapsed after platinum-based chemotherapy (3 of them also received paclitaxel and another 2 received tamoxifen). Four patients relapsed after carboplatin and paclitaxel, one of whom was treated with topotecan thereafter. Two patients relapsed after single-agent paclitaxel. Two patients with advanced disease and poor performance status without previous treatment received only goserelin. There was one complete response (6.7%) and 1 partial response (6.7%) lasting 8 and 14 months respectively (overall response rate 13.4%). In addition, the disease stabilized in three patients (20%) for a median of 7.5 months. In 10 patients the disease progressed. There was no significant toxicity. Median survival of all patients was 5.8 months.

Conclusion: Goserelin was helpful in one-third of our patients with advanced and refractory ovarian cancer. It is an easy and non-toxic option for treating very ill or previously heavily treated patients.
 

Background: Coverage of part of a soft tissue defect in the thumb, without bone shortening and without long-lasting immobilization in an inappropriate position leading to stiffness, is difficult to achieve.

Objectives: To report our experience using Foucher’s modification of the first dorsal metacarpal artery flap for thumb reconstruction in 21 cases.

Methods: Foucher’s flap is based on the neurovascular structures of the first dorsal metacarpal artery flap and radial nerve-sensitive branches on the dorsum of the second metacarpal and proximal phalanx. The cause of injury was work-related in all 21 cases. The patients' mean age was 37 (range 17–68 years), and mean follow-up was 19 months (range 12–31). Emergency surgery was performed in 13 patients, with a time delay after injury of 4–12 hours. The minimum defect was 12–18 mm and the maximum 20–40 mm. Pedicular length was 55–95 mm. A skin bridge was left intact in 16 cases. In two cases of early postoperative venous congestion and flap loss, a cross-finger flap was performed as a salvage procedure.

Results: Subjective satisfaction score was 8.37/10 (range 4–10); cold intolerance was experienced in 60% and dysesthesia in 33%. All except one patient are able to use their thumb in daily activity. Loss of mobility in the proximal interphalangeal joint of the index finger was less than 20 degrees. Semmes-Weinstein sensitivity evaluation score was 3.61–4.31 on the flap and 0–6.65 on the donor site. Two-point discrimination was 10.8 mm (range 8–20). Grip strength was reduced by 15% compared to the unaffected hand (hand dominance was not taken into consideration). Rehabilitation was not consistent as almost all the patients were living in another location.

Conclusions: First DMCA[1] pedicle flap is a successful thumb reconstruction method, especially in patients not disturbed by its cosmetic appearance.

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[1] DMCA = dorsal metacarpal artery

Background: Multiple factors are involved in the pathogenesis of hypertension in the obese individual.

Objective: To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.

Methods: We evaluated three groups: 25 obese hypertensive patients (age 45.7±1.37 years, body mass index 34.2±1.35 kg/m², systolic/diastolic blood pressure 155±2.9/105±1.3, mean arterial pressure 122±1.50 mmHg); 21 obese normotensive patients (age 39.6±1.72, BMI[1] 31.3±0.76, SBP/DBP[2] 124±2.1/85.4±1.8, MAP[3] 98.2±1.80); and 17 lean normotensive subjects (age 38.1±2.16, BMI 22.1±0.28, SBP/DBP 117±1.7/76.8±1.5, MAP 90.1±1.50). We determined basal resting metabolic rates, plasma insulin (radioimmunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n=14) and 14 (n=10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx[4] (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.

Results: Obese hypertensive patients had significantly higher basal RMR[5] and plasma NE[6] levels. Insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than that of obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP⁵, RMR, and plasma NE and insulin .Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.  

Conclusions: A reduction of sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.

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[1] BMI = body mass index

[2] SBP/DBP = systolic blood pressure/diastolic blood pressure

[3] MAP = mean arterial pressure

[4] UNOx = urinary nitric oxide

[5] RMR – resting metabolic rate

[6] NE = norepinephrine

This review summarizes the clinical, metabolic and genetic characteristics of early-onset type 2 diabetes in Mexico. Early-onset type 2 diabetes is both a clinical challenge and a public health problem. It is calculated that almost 300,000 Mexican diabetics are diagnosed between the ages of 20 and 40. The large Mexican family structure and the high prevalence of the disease provide a unique opportunity to identify the genes and the metabolic abnormalities involved in this form of the disease. In a hospital-based population, our group found that insulin deficiency was the main defect in this form of diabetes. Mutations in the HNF-1α or HNF-4α genes or autoimmunity to the beta cell were found in a small proportion of cases, leaving unexplained the majority of cases. Also discussed are the epidemiologic and therapeutic implications of early-onset type 2 diabetes, and the possible role of genetic testing for prevention.

Background: Open reduction and internal fixation are the current trends of treatment for comminuted calcaneal fractures. Assessing treatment results is often difficult due to discrepancy between objective parameters such as range of movement, and subjective results such as pain.

Objectives: To test the reliability of footprint analysis as an adjuvant method of postoperative assessment of patients who sustained calcaneal fractures.

Methods: Dynamic and static footprint analysis was used as an adjuvant method to objectively assess operative results. This method is simple and is independent of the patient’s initiatives. This modality was used in 22 patients followed-up 9–90 months postoperatively.

Results: We found a good correlation between footprint analysis and objective and subjective parameters of results expressed by the American Orthopedic Foot and Ankle Society hind foot score. In certain cases, this method can be used to distinguish between uncorrelated parameter results, such as malingering, and workmens’ compensation claims.

Conclusion: We recommend the use of this simple, non-invasive objective test as an additional method to assess the results of ankle and foot surgery treatment.