Breast milk and adipose tissue fatty acid composition in relation to maternal dietary intake

The fatty acid (FA) relative concentration (g/100g) of human milk triglyceride (TG) was compared to that of adipose tissue (AT). A high concentration of linoleic acid (C-18:2) was present in AT, probably reflecting long term high linoleic acid dietary intake. Linoleic acid was slightly lower in colostrum and transitional milk. No difference in C-18:2 relative concentration was seen between AT and human milk obtained 6 weeks post-partum. Marked short-term dietary modification in linoleic acid intake of the mother, 6 weeks post-partum, did not result in changes in C-18:2 relative concentration of human milk. In spite of measured marked intradiurnal variability in C-18:2 intake, human milk TG FA relative concentration remained remarkably constant. It is suggested that human milk TG FA composition reflects, mainly, the composition of AT. With the increased dietary intake of polyunsaturated fat in many populations, high levels of linoleic acid in human milk are to be expected. The intake of this fatty acid may exceed the suggested daily allowance and thus cause harmful effects, particularly in preterm infants.     

Standard and Nonstandard Applications of Sentinel Node-guided Melanoma Surgery

Identification and histologic study of the sentinel node (SN) is an acceptable, yet not firmly established, guide for treating intermediate-thickness melanoma. This study widens the range of applications of this technique. We included 97 patients with intermediate-thickness melanoma lesions or lesions for which there is no standard treatment. Fifty-six underwent preoperative lymphoscintigraphy, and all underwent intraoperative lymphatic mapping (IOLM) using blue dye, followed by frozen section study and total node processing by serial sections. Elective lymph node dissection was performed in cases of metastasis to the sentinel node or technical failures with high risk. Four categories were defined: (A) intermediate-thickness lesions (mean 2.27 mm) (n= 45); (B) thin lesions (mean 1.14 mm) with risk factors of regional failure (n= 27); (C) lesion thickness close to but more than 4 mm (n= 10); and (D) lesions of undetermined thickness (n= 15). Median follow-up was 30 months (range 13–51 months). Intraoperative lymphatic mapping successfully identified the sentinel node (SN) in 93% of basins explored. Metastases were detected in 11 SNs. There were three lymph basin recurrences in patients with previously negative SNs, all salvaged by therapeutic lymph basin dissection and are NED (no evidence of disease). Two SN⁺ patients had systemic recurrences; one died of his disease, and the other is alive with disease. One SN⁻ patient died NED owing to other cause. This technique spared 83% of category A patients from lymph node dissection. It allowed better staging and better decision making for treatment in categories B and D; and it prevented early regional recurrences in category C patients. Intraoperative lymphatic mapping with SN guidance is a novel, low-morbidity approach applicable and advantageous for a wide range and subgroups of melanoma patients.     

Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor.

PURPOSE: To investigate the safety and tolerability and to explore the pharmacokinetic and pharmacodynamic profile of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with solid tumors that express epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: This was a phase I dose-escalation trial of EMD72000 in patients with advanced, EGFR-positive, solid malignancies that were not amenable to any established chemotherapy or radiotherapy treatment. EMD72000 was administered weekly without routine premedication until disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were treated with EMD72000 at five different dose levels (400 to 2,000 mg/wk). National Cancer Institute common toxicity criteria grade 3 headache and fever occurring after the first infusion were dose limiting at 2,000 mg/wk; thus, the maximum-tolerated dose was 1,600 mg/wk. No other severe side effects, especially no allergic reactions or diarrhea, were observed. Acneiform skin reaction was the most common toxicity, but it was mild, with grade 1 in 11 patients (50%) and grade 2 in three patients (14%). Pharmacokinetic analyses demonstrated a predictable pharmacokinetic profile for EMD72000. Pharmacodynamic studies on serial skin biopsies revealed that EMD72000 effectively abrogated EGFR-mediated cell signaling (eg, reduced phosphorylation of EGFR and mitogen-activated protein kinase), with no alteration in total EGFR protein. Objective responses (23%; 95% CI, 8% to 45%) and disease stabilization (27%; 95% CI, 11% to 50%) were achieved at all dose levels, and responding patients received treatment for up to 18 months without cumulative toxicity. CONCLUSION: Treatment with EMD72000 was well tolerated and showed evidence of activity in heavily pretreated patients with EGFR-expressing tumors. EMD72000 at the investigated doses significantly inhibited downstream EGFR-dependent processes.     

Increased risk of salivary gland tumors after low-dose irradiation

Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow-up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.     

Susac syndrome.

OBJECTIVE: The objective of this study was to describe the clinical manifestations; radiographic, audiometric, and retinal fluorescein angiography findings; pathogenesis and treatment of Susac syndrome with review of the literature. STUDY DESIGN: We conducted a retrospective case review. SETTING: This study was conducted at a tertiary referral center. PATIENT: A 50-year-old woman presented with recurrent episodes of neurologic symptoms, bilateral sensorineural hearing loss, and silent retinal artery occlusion. INTERVENTIONS: The patient underwent complete evaluation, including magnetic resonance image studies, audiometric tests, and retinal fluorescein angiography. She was treated initially with corticosteroids and later with other immunosuppressive agents. RESULTS: The patient was initially diagnosed with left sudden sensorineural hearing loss. Despite comprehensive clinical and laboratory studies that did not reveal systemic disease, 3 weeks later, the patient developed vertigo, sensorineural hearing loss, and tinnitus in the opposite ear. The neurologic involvement and the bilateral audiologic manifestations raised the possibility of Susac syndrome. CONCLUSION: Susac syndrome is a rare disorder of unknown origin characterized by the triad of encephalopathy, fluctuating hearing loss, and visual loss resulting from microangiopathy of the brain, cochlea, and retina. The multiple organ involvement seen in Susac syndrome raises a differential diagnosis ranging from autoimmune disease, through systemic vasculitis, to multiple sclerosis. Otolaryngologists should be aware of this syndrome as a result of the vestibulocochlear manifestations and the multidisciplinary evaluation that is required.     

Computer-assisted medication review for asthmatic patients as a basis for intervention Constructing and validating an algorithmic computer instrument in pharmacy practice

OBJECTIVE: To construct and validate a computer instrument that identifies asthma patients receiving--theoretically--suboptimal drug therapy in community pharmacies, by the use of patient medication records. This selection enables the pharmacist to assist these patients in using medicines appropriately. METHODS: According to Dutch asthma guidelines which describe a stepwise approach and in order to define correct profiles for the use at each level of these guidelines, the optimum use of drugs in the different levels in asthma treatment was expressed in defined daily doses (DDDs) per pharmacological drug-group during a period of one year. An algorithmic computer instrument was developed to select patients with medication use deviant from these profiles. By using nine different selection profiles, the computer instrument stratified patients according to the medication records filed in the pharmacy computer. Patient medication records in four community pharmacies were investigated to validate the selection profiles as indicators for theoretically suboptimal drug use by asthma patients. The validation was performed by comparing the professional judgement of participating pharmacists with the selections made by the computer. MAIN OUTCOME MEASURE: Positive predictive value and negative predictive value of the selection made by algorithmic computer instrument. Rate of false-positive results. RESULTS: The computer instrument identified asthma patients using theoretically suboptimal drug therapy with approximately 95% predictive value compared with the professional judgement of the pharmacists. The rate of false-positive results was 5%. CONCLUSION: The results of the algorithmic computer instrument and the professional judgement of the pharmacists are in close agreement. The instrument will be utilised in further research in the IPMP study (Interventions on the principle of Pulmonary Medication Profiles) investigating the role of Dutch community pharmacists in counselling patients who are at risk of suboptimal drug use in the treatment of their asthma.