Current Concepts in Osteoradionecrosis after Head and Neck Radiotherapy.

Osteoradionecrosis (ORN) of the jaws is a feared complication of head and neck radiotherapy. ORN causes significant morbidity for patients and controversy among clinicians. This overview considers the variations in definition and classification of the condition that affect estimates of incidence and also the interpretation of evidence. The influence of newer radiotherapy techniques in reducing ORN through reduced dose and xerostomia is balanced against a probable increase in a vulnerable population through a rising head and neck cancer incidence. Theories of pathophysiology of ORN include radiation-induced osteomyelitis, hypoxic and hypovascular theory and fibroatrophic theory. Prevention strategies include restorative dentistry and radiation planning techniques. Treatments range from conservative 'watch and wait' through to more radical surgical strategies. Newer medical management strategies are available with a limited evidence base. The use of hyperbaric oxygen therapy remains controversial and the background and need for newer hyperbaric oxygen trials is discussed.

'I've got hay-fever and my mouth is stinging!'.

A case of oral allergy syndrome is presented. Crossreactivity of pollens with some fruit/vegetables causes immediate IgE-mediated symptoms localised to the mouth. Diagnosis is suspected from positive skin prick testing in the presence of a suggestive history. Management is by allergen avoidance. In serious and refractory cases, referral to a regional allergy clinic is recommended.

The law of unintended consequences in action: increase in incidence of hypokalemia with improved adequacy of dialysis.

In 1996, we raised our peritoneal dialysis (PD) dose to meet new DOQI adequacy targets. Concurrently, we noted an increase in the frequency of K+ levels below 3.5 mEq/L. A continuous quality improvement (CQI) project was initiated to quantify the impact of increasing dialysis dose on the prevalence of hypokalemia in our unit. Measurements of serum K+, blood urea nitrogen (BUN), creatinine, residual renal function, and the number and type of clinical interventions required to maintain eukalemia were abstracted from the charts of 62 patients enrolled in our program for more than 6 months and having more than two adequacy data points. In the seven consecutive 6-month periods from January 1996 to June 1999, dialysis dose progressively increased while median serum K+ decreased, and the percentage of patients requiring either diet counselling or K+ supplementation rose from 9% to 42%. We conclude that the increased clearance of K+ that occurs with increasing dialysis dose may lead to significant hypokalemia in a large proportion of PD patients dialyzed to DOQI adequacy targets. Maintenance of eukalemia in this population often requires increased K+ intake and or oral supplementation. Further studies are needed to ascertain whether the prevalence of hypokalemia is sufficient to warrant routine addition of K+ to PD dialysis solutions.

Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy.

OBJECTIVE: To determine the incidence and prognostic significance of documented eradication of breast cancer axillary lymph node (ALN) metastases after neoadjuvant chemotherapy. SUMMARY BACKGROUND DATA: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer and is being evaluated in patients with earlier-stage operable disease. METHODS: One hundred ninety-one patients with locally advanced breast cancer and cytologically documented ALN metastases were treated in two prospective trials of doxorubicin-based neoadjuvant chemotherapy. Patients had breast surgery with level I and II axillary dissection followed by additional chemotherapy and radiation treatment. Nodal sections from 43 patients who were originally identified as having negative ALNs at surgery were reevaluated and histologically confirmed to be without metastases. An additional 1112 sections from these lymph node blocks were obtained; half were stained with an anticytokeratin antibody cocktail and analyzed. Survival was calculated using the Kaplan-Meier method. RESULTS: Of 191 patients with positive ALNs at diagnosis, 23% (43 patients) were converted to a negative axillary nodal status on histologic examination (median number of nodes removed = 16). Of the 43 patients with complete axillary conversion, 26% (n = 11) had N1 disease and 74% (n = 32) had N2 disease. On univariate analysis, patients with complete versus incomplete histologic axillary conversion were more likely to have initial estrogen-receptor-negative tumors, smaller primary tumors, and a complete pathologic response in the primary tumor. The 5-year disease-free survival rates were 87% in patients with preoperative eradication of axillary metastases and 51% for patients with residual nodal disease after neoadjuvant chemotherapy. Of the 39 patients with complete histologic conversion for whom nodal blocks were available, occult nodal metastases were found in additional nodal sections in 4 patients (10%). At a median follow-up of 61 months, the 5-year disease-free survival rates were 87% in patients without occult nodal metastases and 75% in patients with occult nodal metastases. CONCLUSIONS: Neoadjuvant chemotherapy can completely clear the axilla of microscopic disease before surgery, and occult metastases are found in only 10% of patients with a histologically negative axilla. The results of this study have implications for the potential use of sentinel lymph node biopsy as an alternative to axillary dissection in patients treated with neoadjuvant chemotherapy.

Local recurrence and survival among black women with early-stage breast cancer treated with breast-conservation therapy or mastectomy.

BACKGROUND: Black women with breast cancer have significantly worse survival rates and receive diagnoses at relatively younger ages, compared with white patients with breast cancer, in the United States. Young age at diagnosis has been associated with increased risk for local recurrence (LR) after breast-conservation therapy (BCT). The goal of this study was to evaluate the impact of age and BCT on LR and survival rates among black patients with breast cancer. METHODS: The records for 363 black women treated for breast cancer (excluding stage IV disease) at a comprehensive cancer center were reviewed. RESULTS: Fifty-eight percent of patients (n = 211) had tumors < or = 5 cm in diameter. Forty-two of these patients (19.9%) received BCT; the LR rate for this group was 9.8%. A total of 168 patients (79.6%) underwent mastectomy; the LR rate for this group was 8.9%. Data on the primary operation were unavailable for one patient. Five-year disease-free survival rates were similar for patients treated with BCT and those treated with mastectomy (88% and 73%, respectively). LR was associated with significant decreases in 5-year overall survival rates for both the BCT group (67% vs. 95%, P < .01) and the mastectomy group (43% vs. 76%, P < .01). LR and 5-year disease-specific survival rates were similar for patients <50 years of age and patients > or = 50 years of age, regardless of treatment. CONCLUSIONS: LR and survival rates are not compromised by the use of BCT among black American patients. LR is associated with an increased risk of breast cancer death, regardless of treatment type. Younger age at diagnosis was not associated with an increased rate of LR after BCT in this series.

Occurrence of the chromoplast protein ChrA correlates with a fruit-color gene in Capsicum annuum.

Plant geneticists have determined that the color of ripe fruits of sweet peppers (Capsicum annuum L.) is determined by four genes: y, c1, c2 and cl. We have compared the electrophoretic behavior of chromoplast membrane proteins of seven varieties of C. annuum which differ in these genes. ChrA was detected only in the varieties that had a y+ genotype, and was not affected by variations in the other three genes. The identity of ChrA was verified by probing blots of SDS gels with antiserum to ChrA. The second known chromoplast-specific protein, ChrB, was found to be independent of all four genes. No proteins correlating with c1, c2 or cl were detected in either one- or two-dimensional gels.

Effects of amlodipine on myocardial infarction, infarct expansion, and ventricular geometry in the rat.

Infarct expansion remains an important sequela of myocardial infarction. Both angiotensin converting enzyme inhibitors and intravenous nitrates reduce early infarct expansion in humans. This is believed to be caused by the reduction in left ventricular systolic wall stress that results from the arteriolar vasodilatation they produce. Patients are frequently already receiving calcium channel blockers at the time of infarction or these drugs are sometimes administered in the perimyocardial infarction period. The calcium blockers of the dihydropyridine class might be expected to modify infarct expansion. However, their effect on this process has not been studied. We therefore evaluated the effect of early treatment with the calcium blocker amlodipine, a potent arteriolar vasodilator with minimal negative inotropic properties, on chronic myocardial infarction in the rat. Permanent left coronary occlusion was created after pretreatment with amlodipine, 0.25 mg/kg (low dose) or 1.0 mg/kg (high dose), or placebo, intravenously twice a day, and continued for 7 days after infarction. Hearts (n = 50) were perfusion fixed 21 days after infarction and analyzed for infarct extent, scar thickness, left ventricular shape and size, and expansion index. Both doses decreased mean blood pressure (119 +/- 3 to 99 +/- 5 mm Hg low dose, p = 0.004; 110 +/- 5 to 84 +/- 4 mm Hg high dose, p = 0.0003), with reflex tachycardia only after the high dose (heart rate 395 +/- 9 to 434 +/- 11, p = 0.001). Infarct extent was equal in the three groups (39 +/- 2%, 41 +/- 2%, and 41 +/- 3% of left ventricular circumference for control, low, and high doses, respectively). The three groups did not differ significantly with regard to left ventricular cavity cross-sectional area (80 +/- 4, 77 +/- 3, and 87 +/- 3 mm2, control, low, and high doses, respectively; p = 0.07 high dose vs control), mean scar thickness (0.74 +/- 0.06, 0.73 +/- 0.05, and 0.65 +/- 0.06 mm, control, low, and high doses, respectively; p = NS), and expansion index (1.52 +/- 0.10, 1.58 +/- 0.12, and 1.95 +/- 0.19, control, low, and high doses, respectively; p = 0.08 high dose vs control). In the subgroup with larger infarcts (infarct extent greater than 0.39 of left ventricle), the expansion index was higher in the high-dose group (2.37 +/- 0.23 vs 1.64 +/- 0.17 control; p = 0.04). In this model, treatment with amlodipine does not limit infarct extent or reduce early infarct expansion and left ventricular dilatation, even when initiated before infarction.(ABSTRACT TRUNCATED AT 400 WORDS)

Nutrition-related backgrounds and counseling practices of doctors of chiropractic.

A questionnaire was designed and mailed to the entire membership (no. = 438) of the San Francisco Bay Area Chiropractic Society to determine their nutrition education backgrounds and counseling practices and the relationship of backgrounds and counseling practices and the relationship of backgrounds and information resources to counseling practices. Results, based on the 23% response rate, indicated that the hours of formal nutrition education in chiropractic college varied widely in the five categories of responses from zero to more than 120, with the median respondent falling in the median category (81 to 100 hours). Sixty percent of the respondents indicated that they provided nutrition information to their patients on a routine basis, and 38% provided information on request only. The major forms of nutrition information dissemination were counseling (87%) and written materials (74%). The majority of respondents reported that they diagnose osteoporosis, arthritis, and allergies and use nutrition treatments for those disorders as a part of overall therapy. Chiropractic journals and texts were the most frequently used sources of nutrition information. Awareness of the educational backgrounds of registered dietitians correlated positively with the use of dietitians as a resource for nutrition information (p less than .005). The survey results suggest a need for dietitians to become involved in the nutrition-related practices of chiropractors as sources for information and referral.

Low blood selenium levels in patients with cystic fibrosis compared to controls and healthy adults.

Frank clinical selenium deficiency has been described in cystic fibrosis (CF), and a relative deficiency has been proposed as contributing to the pathogenesis of the disease. Because of these possibilities, we investigated the relationship between overall nutritional status in CF with measures of selenium nutriture. Fifteen stable outpatients with CF (group I) were compared to 13 age-matched controls (group II) and 27 healthy adults (group III). Whole blood, plasma, and red blood cell selenium levels were reduced by 31%, 29%, and 33%, respectively, in CF patients vs controls (all p less than 0.001). In addition, both groups I and II showed significantly lower blood selenium levels than healthy adults (p less than 0.005). Nutritional assessment revealed CF patients to be undernourished, with significant decreases in serum albumin (p less than 0.025), weight-for-height deficit (p less than 0.01), and weight-for-age (p less than 0.025) vs controls. However, only the triceps skinfold (TSF) measurement correlated significantly with selenium status (r = 0.56: p less than 0.05 for whole blood selenium vs TSF). We conclude, based on the magnitude of decrement in blood selenium, that it is unlikely that selenium plays a significant primary pathogenic role in cystic fibrosis. However, these patients are at high risk for developing clinical selenium deficiencies. The measurement of blood selenium levels using appropriate age-matched normal standards should be mandatory in all CF patients with malnutrition, or in those requiring parenteral nutritional support.

Myodegeneration in Kentucky white-tailed deer.

Skeletal or cardiac myodegeneration, or both, was observed in 4 free-ranging female white-tailed deer that were found dead or recumbent and unable to rise. Gross pathologic findings included white or chalky streaks in heart or skeletal musculature. Degeneration, necrosis, and mineralization were observed microscopically in affected striated muscles. Although the precise cause of myodegeneration was not determined, changes were considered compatible with nutritional or exertional myopathy.

The folate in human milk.

In previous studies of the folate content of human milk, samples were prepared for assay by a method that resulted in a turbid solution that was then assayed by a turbidimetric microbiological method. We have used an improved microbiological assay in which the milks were treated with rennin to precipitate casein and heated in a buffered ascorbate to coagulate lactalbumin and lactoglobulin. Milks were obtained serially from nursing mothers for periods ranging from 1 day to 6 months postpartum. The results showed that the folate in human milk has few glutamate residues since treatment with a purified folate conjugase preparation release no additional folate activity for Lactobacillus casei. Colostrum is relatively low in folate, but milk folate increases as lactation proceeds. During each stage of lactation there was great variation in milk folate content among the women. In the case of a folate-deficient woman, supplementation with folic acid resulted in a prompt increase in milk folate level.

Riboflavin deficiency in women taking oral contraceptive agents.

The effect of oral contraceptive agents (OCA) on riboflavin nutritional status of women of child-bearing age in a low socioeconomic population was studied. For a control group, 100 women in the same age and socioeconomic group using alternate forms of contraception were selected. Riboflavin deficiency was determined by measuring erythrocyte glutathione reductase activity, a reliable index of the deficiency. None of the women was on vitamin supplements or had clinical conditions effecting dietary intake or utilization. Eleven of 100 women in the control group had biochemical evidence of deficiency. This compared to 24 of 56 OCA users who were deficient. The frequency of deficiency increased among those on OCA for longer periods of time. Thirteen of 17 OCA users for 3 years or more, compared to 11 of 39 users under 3 years were deficient. There were no discernable dietary differences between the groups. These studies demonstrate that riboflavin deficiency is a problem of women in the lower socioeconomic level in the child-bearing age. The use of OCA aggravates the prevalence of deficiency.