Remission rates following preoperative chemotherapy and radiation therapy in patients with breast cancer.

PURPOSE: To evaluate remission and breast-conservation rates after preoperative chemotherapy or chemo-radiotherapy (CT-RT). PATIENTS AND METHODS: Seventy-three patients with 74 biopsy-proven invasive breast cancers prospectively entered the protocol. Eighteen patients were treated by neoadjuvant chemotherapy followed by surgery and adjuvant irradiation (chemotherapy group). Fifty-five patients with 56 tumors were treated with combined neoadjuvant chemo-radiotherapy, followed by surgery (chemo-radiotherapy group). Most patients of both treatment groups received 4 cycles of EC chemotherapy. In some patients with large tumors 3 cycles of CMF were added. Chemotherapy was followed by hormonal treatment with tamoxifen or LHRH agonists in case of positive hormone-receptor status. Preoperative radiotherapy was administered using 2 Gy fractions up to a total dose of 50 Gy, followed by a tumor boost of 6 to 11 Gy. The median overall treatment time was 41 days (range: 35 to 55 days). The median time interval between end of neoadjuvant therapy and surgery was 11 weeks (range: 10 to 22 weeks) and 27 weeks (range: 11 to 41 weeks) for the chemotherapy- and chemo-radiotherapy group. The median time interval between end of chemotherapy and the beginning of irradiation ranged between 2 and 8 weeks (median 4 weeks) in the chemo-radiotherapy group. RESULTS: Side-effects due to chemo- or radiotherapy were moderate and reversible. In the chemotherapy group 17/18 patients (94%) achieved a partial (pPR) and 1/18 patients (6%) a complete histopathological response (pCR). In the chemo-radiotherapy group 32/56 (57%) showed a pPR and 24/56 (43%) a pCR. The difference in complete remission is significant (Fisher's Exact Test: p = 0.004). In 45/74 cases (61%) the breast was preserved, immediate breast reconstructions with rectus myocutaneous flaps (TRAM) after mastectomy were performed in 8/74 cases (11%) and modified radical mastectomies without reconstruction were required in 21/74 cases (28%). The breast conservation rates were similar in both treatment groups. CONCLUSIONS: Even though the small number of patients in the present protocol does not permit definite conclusions, the results of combined modality treatment seem promising with regard to tumor remission within the treated breast and as a tool for breast conservation in advanced stage disease. On the basis of these encouraging data a prospective Phase-III study has been initiated.

Child abuse in an infant presenting as unexplained acute systemic hypertension.

Hypertension in the infant is uncommon and is usually associated with renal vascular or parenchymal disease, coarctation or thrombosis of the aorta, or chronic lung disease. A 3-month-old infant who presented with unexplained acute systemic hypertension was subsequently discovered to have an undiagnosed femoral fracture secondary to child abuse. Undiagnosed fractures, which are often associated with child abuse, should be considered in the differential diagnosis of an infant presenting with unexplained systemic hypertension.

Prevalence of stress hyperglycemia among patients attending a pediatric emergency department.

OBJECTIVE: To determine the prevalence and clinical characteristics associated with stress hyperglycemia among children and adolescents attending a pediatric emergency department. DESIGN: Patients who required a venipuncture for evaluation of an acute illness or injury from October 1992 to March 1993 in an urban pediatric emergency department were enrolled and screened prospectively for hyperglycemia (glucose level > or = 8.3 mmol/L; > or = 150 mg/dl). Data were collected regarding demographic characteristics, history, clinical findings, and admission status. RESULTS: A total of 926 patients ranging in age from 3 days to 21 years were enrolled. Blood glucose values ranged from 1.94 mmol/L (35 mg/L) to 14.65 mmol/L (264 mg/dl); 35 patients (3.8%) had hyperglycemia. The prevalence of stress hyperglycemia was significantly increased among patients if they (1) had temperatures greater than 39.5 degrees C (9.3%) versus normal temperatures (2.8%) (p < 0.001), (2) had been admitted to a critical care unit of the hospital (24.1%) or to any hospital unit (4.4%) versus not having been admitted (2.6%) (p < 0.001), and (3) had received fluids intravenously (6.0%) versus having received no fluids intravenously (2.7%) (p = 0.014). CONCLUSIONS: Stress hyperglycemia is a frequent clinical occurrence in a pediatric emergency department. It does not appear to be associated with a particular diagnostic category but is significantly associated with severity of illness as measured by elevated temperature, hospital admission, and hydration status.

Anophthalmia, cleft lip/palate, facial anomalies, and CNS anomalies and hypothalamic disorder in a newborn: a midline developmental field defect.

We describe an infant with a unique pattern of midline defects, including anophthalmia, cleft lip and palate, macrocephaly, cutis aplasia, and micrognathia. CNS anomalies including massive hydrocephalus with destruction of most recognizable structures were observed. The infant also developed panhypopituitarism, diabetes insipidus, and a seizure disorder. We postulate that this patient could represent a more complex form of the Delleman syndrome or a new morphogenetic syndrome secondary to ventral induction with extension to the developmental fields of the first and second branchial arches.

Magnesium, zinc and copper in plasma and blood cellular components in children with IDDM.

The levels of magnesium (Mg), zinc (Zn) and copper (Cu) in the plasma, erythrocytes (RBC) and polymorphonuclear (PMN) and lymphocyte (L), leukocytes (WBC) of 45 diabetic children were compared to those of 12 normal children and were related to the diabetic control via HbA1 and fasting blood sugar (FBS) assessments. Mineral levels were determined via Zeeman-effect atomic absorption spectrophotometry following separation of plasma, RBC, and WBC fractions (PMN vs. M). ANOVA (four-way, blood components, by two-way, diabetic vs. normal children) was significant for Mg only (F = 4.60, P < 0.004). Plasma Mg and M-WBC Mg were significantly lower in children with diabetes (780 +/- 16 vs. 860 +/- 29 mumol/l and 519 +/- 33 vs. 866 +/- 86 micrograms/10(10) cells, respectively). RBC Zn was significantly lower in diabetic youngsters by t-test (0.48 +/- 0.012 vs. 0.57 +/- 0.046 per mumol/g Hgb, t = 2.79, P < 0.004), but the ANOVA for Zn was not significant. Cu level differences were not significant. HbA1 was predicted only by PMN-WBC Mg (F = 8.78, P < 0.04) and FBS by none. In conclusion, the mineral status of these diabetic children was altered in regard to Mg, but was mainly independent of diabetic control.

Osteoporosis as the presenting sign of leukemic relapse in an adolescent: case report and literature review.

Osteoporosis in adolescence is rare and usually secondary to an underlying disease process whose diagnosis may be difficult to detect. Osteoporotic vertebral collapse is an uncommon presenting sign of acute lymphoblastic leukemia (ALL). We describe a 13-year-old boy with osteoporotic vertebral collapse secondary to relapse of ALL whose blood count and blood morphology were normal but whose 1,25 = (OH2) = vitamin D level was deficient. A combination of chemotherapy, calcitriol and calcitonin therapy was successful in reversing the process. His case is presented to describe the diagnostic and therapeutic issues involved.

Comparative heights of mothers and fathers whose children are short.

This study was designed to investigate and compare the heights of mothers and fathers whose children had various forms of short stature. The heights of parents of a total of 341 children were grouped by their children's diagnoses into three groups: group 1, genetic short stature; group 2, a constitutional delay of growth; and group 3, normal "short" stature (children in the fifth to 25th percentile). Analysis indicated that the data were gaussian in distribution and that no significant skewing or kurtosis was noted in any group for either maternal or paternal heights. The mean height of mothers in group 1 (mean +/- SD, 157.7 +/- 6.8 cm) was less than (F = 14.36) the mean height of mothers in either group 2 (mean +/- SD, 161.1 +/- 6.9 cm) or group 3 (mean +/- SD, 162.5 +/- 6.6 cm). In contrast, the mean heights of fathers were not significantly different (F = 2.13) among the three groups (mean +/- SD, 173.3 +/- 7.5, 173.8 +/- 8.3, and 176.0 +/- 9.6 cm). Thus, a significant shift to greater shortness in mothers' heights than in fathers' heights for the parents of children with genetic short stature was noted. Such a differential shortness was not detected in the parents of children with a constitutional delay of growth.

Nipple (papilla) development in girls: III. The effects of pregnancy.

Previous cross-sectional and longitudinal studies of girls have documented that they have a significant growth in nipple size during Tanner stages pubic hair (PH)4 and PH5 or breast (B)4 and B5. This study assesses whether there is any effect of pregnancy on nipple development in adolescent girls. Thirty-three pregnant girls were compared to a previously reported group of 390 girls who were not pregnant. Of the 33 girls, ten were followed longitudinally for a period of nine to 79 months, during which time they became pregnant. In each girl, nipple diameter was measured and the Tanner stage assessed. A markedly significant increment in nipple size was noted in the girls who were pregnant (pregnancy nipple size 12.6 mm vs. PH5 9.7 mm and B5 9.9 mm). Comparison of ten girls prior to and during pregnancy revealed a significant increment as well (10.2 mm vs. 12.8 mm, respectively). Pregnancy provides a further stimulus for nipple development in girls beyond that which occurs during normal puberty.

Nipple (papilla) development in puberty: longitudinal observations in girls.

The purpose of this study was to determine the manner of breast nipple (papilla) development occurring during puberty in girls on a longitudinal basis and to compare this development to the established criteria of sexual maturation. Forty-six girls (19 white and 27 black) were followed for periods of 2 to 5 years (mean 2.67 years). In each, the nipple diameter was measured and the Tanner stage assessed. Minimal nipple development occurred from stages PH1 to PH3 (3.24 to 4.44 mm) and B1 to B3 (3.00 to 4.72 mm) or more than 1 year prior to menarche (3.75 mm). Significant growth occurred beyond stages PH3 (PH4 6.54 mm, PH5 8.98 mm) and B3 (B4 7.25 mm, B5 9.41 mm) and from less than 1 year prior to menarche to more than 1 year after menarche (5.92 mm for girls less than 1 year premenarche, 7.88 mm for girls in their first year after menarche, and 9.05 mm for girls more than 1 year beyond menarche). A more objective definition for breast stages B4 and B5, based upon nipple diameter, is now feasible. Thus, these data enhance the precision with which physiologic events occurring toward the close of puberty in girls can be studied.

Papilla (nipple) development in puberty. The adolescent male.

Papilla (nipple) development was studied in 230 males (119 black, 111 white) aged 3-29 years to compare this development to the established criteria for sexual maturation. Comparison was also made with a previous study of female nipple development to determine whether or when any differences between male and female nipple development occurred. Our male subjects were further assessed to determine if nipple size differed in the presence or absence of gynecomastia. Significant nipple development occurred between pubic hair stages PH1 (diameter 2.8 mm), PH4 (4.4 mm), and PH5 (5.4 mm). Similarly, there was significant incremental growth between genital stages G1 (3.0 mm), G3 (4.6 mm), and G5 (5.5 mm). Nipple development was similar in both sexes through stage PH3, but significantly diverged at stage PH4 (p less than 0.000001) because of a marked increase in female nipple diameter. Boys with gynecomastia had a significantly larger nipple size than boys who had none (p less than 0.001). Differences in nipple diameter between the sexes and between boys with and without gynecomastia probably result from differences in estrogen levels. Perhaps in the future, it will be possible on the basis of nipple diameter to predict which adolescent boys will have persistent gynecomastia.

Benign galactorrhea/breast discharge in adolescent males probably due to breast self-manipulation.

Three adolescent males presented with nipple discharge. In two boys, the expressed secretion was clinically consistent with galactorrhea. Galactorrhea/breast discharge is a rare complaint in males of any age. Although galactorrhea is commonly associated with a neuroendocrine disorder or drug ingestion, the work-up in each, including basal prolactin level, was normal. Reluctantly, each by admitted to breast self-manipulation to reduce gynecomastia. When the behavior was discontinued, the galactorrhea/breast secretion ceased. Clinicians should be aware of this heretofore undescribed and apparently benign phenomenon. If basal hyperprolactinemia is absent in a male with a breast discharge and a history of breast manipulation, then an extensive work-up is not usually indicated.

Familial third-fourth pharyngeal pouch syndrome with apparent autosomal dominant transmission.

A family is presented in which both siblings and their father had evidence of third-fourth pharyngeal pouch syndrome (DiGeorge syndrome). All three individuals had hypocalcemia and unusual facies. Both infants had truncus arteriosus. One infant had evidence of impaired cell-mediated immunity; the father had a relatively decreased number of T-lymphocytes. The syndrome is uncommon, most cases being isolated, and familial presentations are even rarer. Two recent reports described several affected individuals who also had partial deletions of chromosome 22. Chromosome banding studies in our family were normal. Thus our family demonstrates an autosomal dominant pattern of inheritance, although it cannot be proved that this is a single gene defect. We propose that inasmuch as the presentation of the syndrome is quite varied, thorough family investigation including high-resolution cytogenetic analysis is necessary. Familial cases may be more common and require genetic counseling.

Galactorrhea in the adolescent.

Inappropriate lactation--that which occurs beyond the usual postpartum or breast-feeding period or in the male--has been of medical interest for centuries. There is a suggestion that the first recorded case occurred in the Bible in the Book of Esther wherein Mordecai may have breast-fed his niece Esther [1,2]. The Talmud describes a man who nursed his infant after his wife's death during childbirth [3]. Lactation in virgin women was noted by the early Greeks [4], and Aristotle observed lactation in men [5]. The phenomenon of "witch's milk," seen in the newborn, was described as early as 1684 by Bonetus [6]. The first alleged pediatric case of nonpuerperal lactation was of an 8-year-old girl who was able to suckle her baby brother as reported in the 18th Century by Baudelocque [7]. Subsequently, many other cases of abnormal lactation were described in the 19th and early 20th centuries [7-10]. In the past 15 years, there has been a vast proliferation of cases and studies concerning galactorrhea of both sexes [11]. The advent of the prolactin radioimmunoassay was the single most important factor behind the profusion of these investigations [11-14]. Most recently, attention has focused on the high incidence of pituitary tumors--specifically the prolactinoma--in women and to some degree in men [13,15]. The occurrence of such tumors in children and adolescents is also receiving more attention [16,17]. The purpose of this review is to update the reader on galactorrhea with a specific emphasis on: 1) outlining the various causes of galactorrhea that may be seen in adolescent patients; 2) describing the work-up and management of both the male and female adolescent patient with galactorrhea; and 3) describing what is known about the natural history of galactorrhea. A brief description of the physiology of the hypothalamic-pituitary-breast axis and lactation is also presented.

Short stature and dysmorphism in the child and adolescent female. Diagnostic dilemmas.

The clinician often encounters girls with varying combinations of short stature and subtle dysmorphic features that are compatible with either Turner or Noonan syndrome. A classic case of either syndrome with extensive unmistakable traits is the exception rather than the rule. Six cases are presented to help describe some of the difficulties in differential diagnosis and provide strategies to avert them.

Potential errors in the laboratory diagnosis of paroxysmal nocturnal hemoglobinuria.

In a retrospective study of laboratory tests for paroxysmal nocturnal hemoglobinuria (PNH), the red blood cells of several patients gave conflicting results when different testing procedures were used. To resolve these discrepancies, an examination of the various procedures was undertaken, using sulfhydryl reagent-treated red blood cells as model PNH cells. Rabbit antiserum to human red blood cells was used to sensitize erythrocytes for specific antibody-dependent complement lysis sensitivity tests. Acidified serum and inulin were used in fluid-phase complement activation tests. For the general laboratory, a modification of the sucrose lysis test is described, which can give the relative complement sensitivity and size of an abnormal subpopulation of red blood cells. Considering the results of our patients and the reports in the literature of the association of PNH with a variety of lymphoproliferative and myeloproliferative disorders, it is stressed that testing procedures for PNH be controlled more carefully for a better understanding of the nature of the membrane defect.