Oligosaccharides in human milk during different phases of lactation

Twenty-one oligosaccharides of human milk were quantified by high-performance anion-exchange chromatography. Milk samples were collected from 18 mothers during the first 3 mo of lactation. The data show that the highest amount of all oligosaccharides is present at day 4 postpartum (20 g l⁻¹) and then decreases by about 20% at day 30 of lactation. The protective role played by these substances against different infectious agents, in different organs and systems of the breastfed baby, is emphasized.     

Female pseudohermaphroditism and inefficient peak bone mass in an untreated subject affected by 21-hydroxylase congenital adrenal hyperplasia

Here we describe a subject with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-CAH), in its classical virilizing form, who presented at birth ambiguous genitalia and subsequently was assigned by the parents as male. At the age of 8 years, he underwent a two-step surgical correction of hypospadia and at 22 years old, uterus and ovaries were removed and a bilateral testicular prothesis was surgically placed in scrotum. He refused any chronic glucocorticoid therapy, that was given only acutely to prevent adrenal crises during stress, trauma surgery or severe illness. The patient is now 38 years old, he is genotypically female but phenotypically male, with high endogenous levels of androgen, all of adrenal origin, and with an apparent male sexual life. He had severe osteopenia, probably due to the lack of estrogen/androgen-induced increase in bone mineral density, although periferal estrogen conversion was normal. His skeletal mass, in fact, normally acquired during adolescence and early adult life, could in this case be inefficient, for the precocious pseudopuberty, that caused an inefficient peak bone mass in adolescence period.     

Oculo-cerebro-cutaneous syndrome: description of a new case

A newborn girl is described with the following multiple congenital anomalies: an orbital cyst, cutaneous appendages, focal hypo-aplasia of the skin and multiple cerebral cysts. This case of oculo-cerebro-cutaneous syndrome is compared with four previously published cases.     

Isolated breast relapse after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia

Unusual sites of relapses following bone marrow transplantation (BMT) for childhood acute lymphoblastic leukemia (ALL) are rarely reported. We report the case of a 16-year-old girl who presented with an isolated right breast relapse 8 months after allogeneic BMT for ALL in second remission. Biopsy showed an ALL infiltrate. Bone marrow and CSF were normal. The girl never showed before extramedullary involvement. She was treated with local radiotherapy and mild systemic chemotherapy. Nine months after breast relapse, she presented an isolated central nervous system relapse. The treatment of isolated extramedullary relapses following BMT is still controversial.     

Clinical heterogeneity in Sanfilippo disease (mucopolysaccharidosis III) type D: presentation of two new cases

Clinical, radiological and biochemical findings of two new cases of Sanfilippo disease, type D are reported. A high percentage of heparan sulfate was found in the urinary glycosaminoglycan pattern and a severe deficiency of N-acetylglucosamine-6-sulfate sulfatase was demonstrated in skin cultured fibroblasts from the patients. One of the patients presented mild intellectual impairment which differentiates him from the other cases described to date.     

Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer: updated results of a multicentric trial

OBJECTIVES: To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade in advanced prostatic cancer. PATIENTS AND METHODS: Previously untreated patients with histologically proven stage C or D (American Urological Association Staging System) disease were randomly allocated to either bicalutamide (B) or goserelin plus flutamide (G+F). After disease progression, patients treated with B were assigned to castration. The primary endpoint for this trial was overall survival. Prostate cancer-specific survival and progression were included among secondary endpoints. RESULTS: In total 108 patients received B and 112 received G+F. At a median follow-up time of 54 months (range 1-89), 151 patients progressed and 113 died. There was no significant difference in the duration of either progression-free or overall survival. Hazards of progression, death and cancer-specific death, corrected by disease stage, tumor grade and baseline PSA level, showed that patients initially assigned to B had a higher risk of progression but a comparable risk of death and cancer-specific death with the exception of patients with G3 tumors who had an increased risk of death). CONCLUSIONS: In patients with well or moderately well differentiated tumors, B monotherapy followed by castration may offer the same survival chance as maximal androgen deprivation. In those patients it thus represents a reasonable choice that can avoid the side effects of androgen deprivation for considerable periods of time.     

Evidence for corticotropin-releasing factor regulation of serotonin in the lateral septum during acute swim stress: adaptation produced by repeated swimming

RATIONALE: Swim stress decreases extracellular serotonin (5-HT) levels in the rat lateral septum, and adaptation to this effect occurs with repeated swimming. Corticotropin-releasing factor (CRF) administered into the dorsal raphe nucleus (DRN) also decreases 5-HT release in the lateral septum, suggesting that CRF may mediate the effects of swim stress. OBJECTIVES: The hypothesis that endogenous CRF mediates the reduction of 5-HT levels in the lateral septum evoked by swim stress and is involved in the adaptation that occurs with repeated swim stress was tested. METHODS: Extracellular 5-HT levels in rat lateral septum were quantified by means of in vivo microdialysis. Extracellular single unit activity was recorded from the DRN. RESULTS: Intracerebroventricular (i.c.v.) administration of a CRF receptor antagonist prevented the ability of swim stress to decrease 5-HT release in the lateral septum. Prior exposure to swim stress reduced the ability of both CRF (i.c.v.) and a subsequent swim stress to decrease lateral septum 5-HT release (cross adaptation). Additionally, the effects of CRF, administered into the DRN, on DR neuronal discharge were attenuated in rats with a history of swim stress. Finally, administration of a CRF receptor antagonist (i.c.v.) between two swim stress sessions restored the neurochemical response to swim stress (i.e., 5-HT levels were reduced during the second exposure to swim). CONCLUSIONS: Endogenous CRF modulates 5-HT transmission during acute environmental stress and is also integral to adaptation of the 5-HT response produced by repeated stress. Modulation of the 5-HT system by CRF during acute stress may underlie certain coping behaviors, while stress-induced adaptation of this effect may be involved in psychiatric manifestations of repeated stress.     

Cellular interactions between axon terminals containing endogenous opioid peptides or corticotropin-releasing factor in the rat locus coeruleus and surrounding dorsal pontine tegmentum

Recent evidence suggests that certain stressors release both endogenous opioids and corticotropin-releasing factor (CRF) to modulate activity of the locus coeruleus (LC)-norepinephrine (NE) system. In ultrastructural studies, axon terminals containing methionine(5)-enkephalin (ENK) or CRF have been shown to target LC dendrites. These findings suggested the hypothesis that both neuropeptides may coexist in common axon terminals that are positioned to have an impact on the LC. This possibility was examined by using immunofluorescence and immunoelectron microscopic analysis of the rat LC and neighboring dorsal pontine tegmentum. Ultrastructural analysis indicated that CRF- and ENK-containing axon terminals were abundant in similar portions of the neuropil and that approximately 16% of the axon terminals containing ENK were also immunoreactive for CRF. Dually labeled terminals were more frequently encountered in the "core" of the LC vs. its extranuclear dendritic zone, which included the medial parabrachial nucleus (mPB). Triple labeling for ENK, CRF, and tyrosine hydroxylase (TH) showed convergence of opioid and CRF axon terminals with noradrenergic dendrites as well as evidence for inputs to TH-labeled dendrites from dually labeled opioid/CRF axon terminals. One potential source of ENK and CRF in the dorsal pons is the central nucleus of the amygdala (CNA). To determine the relative contribution of ENK and CRF terminals from the CNA, the CNA was electrolytically lesioned. Light-level densitometry revealed robust decreases in CRF immunoreactivity in the LC and mPB on the side ipsilateral to the lesion but little or no change in ENK immunoreactivity, confirming previous studies of the mPB. Degenerating terminals from the CNA in lesioned rats were found to be in direct contact with TH-labeled dendrites. Together, these data indicate that ENK and CRF may be colocalized to a subset of individual axon terminals in the LC "core." The finding that the CNA provides, to dendrites in the area examined, a robust CRF innervation, but little or no opioid innervation, suggests that ENK and CRF axon terminals impacting LC neurons originate from distinct sources and that terminals that colocalize ENK and CRF are not from the CNA.     

Resting energy expenditure in diabetic and nondiabetic patients with liver cirrhosis: relation with insulin sensitivity and effect of liver transplantation and immunosuppressive therapy

BACKGROUND: Hypermetabolism, insulin resistance, and diabetes are common in patients with liver cirrhosis. OBJECTIVE: We assessed whether diabetes and insulin resistance influence postabsorptive energy homeostasis in these patients and whether liver transplantation (LTx) and immunosuppressive drugs affect these relations. DESIGN: Twenty-six patients with liver cirrhosis (16 with and 10 without diabetes) were studied with an insulin clamp and indirect calorimetry. Eleven of these subjects were studied 9 mo after LTx to longitudinally assess its effects. To cross-sectionally explore a longer follow-up period, we studied 65 patients 6, 14, and 32 mo after LTx. Seven patients with chronic uveitis (receiving immunosuppressive therapy) and 20 healthy subjects served as control subjects. RESULTS: Diabetic and nondiabetic patients with cirrhosis had insulin resistance (S(I(clamp)); P < 0.03) and higher measured resting energy expenditure (REE) as a percentage of predicted REE than did healthy subjects (107.6 +/- 1.8% compared with 97.4 +/- 2.3%; P < 0.03), and these 2 alterations were associated (R(2) = 0.119, P = 0.0002). The longitudinal study showed an improvement in the 2 variables after LTx, but full restoration was not achieved. The cross-sectional analysis confirmed this observation in patients studied 6 mo (n = 28) after LTx. In patients studied 14 (n = 21) and 32 mo (n = 16) after LTx, S(I(clamp)) and measured REE as a percentage of predicted REE were not significantly different from those in control subjects. CONCLUSIONS: In patients with liver cirrhosis, higher-than-normal postabsorptive REE was associated with insulin resistance regardless of diabetes. This abnormality persisted in patients studied 6-9 mo after LTx but improved simultaneously with the improvement in insulin sensitivity thereafter.     

A phase II study of concomitant hyperfractionated radiation therapy and double dose intra-arterial cisplatin for squamous cell carcinoma of the head and neck

This successor phase II study evaluates the tolerability and efficacy of concomitant hyperfractionated radiation therapy (HFX-RT) and double dose intra-arterial (IA) cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In doing so, this study represents further resurgence of the potential use of IA chemotherapy in the management of SCCHN. This has been enabled by the evolution of angiographic catheter/microcatherter technology. Between 1997 and 1999, 24 patients with locally advanced T4/T3 SCCHN were treated with HFX-RT (76.8- 81.6 Gy at 1.2 Gy bid over 6-7 weeks) and high-dose IA cisplatin (150mg/m2 given at the start of and during RT boost treatment [start of week 6 and 7]). Twenty-two patients (92%) had T4 disease and 14 (58%) N2/ N3 disease. Acute toxicity was limited to two grade 4 (8%) and 19 grade 3 (79%) mucosal events; and single grade 3 hematologic, infectious and skin events. Eight patients (33%) were unable to receive the second planned dose of IA cisplatin. Twenty-two patients had complete response (92%) at the primary site. Among 17 patients with positive neck disease 12 (71%) achieved complete response in the neck. Follow-up ranges from 7-30 months (median = 18 months) with 14 patients alive without disease, 2 alive with disease, 7 dead of disease and 1 dead of intercurrent disease. While concomitant HFX-RT and double dose IA cisplatin as used in this study is associated with encouraging response rates in this highly unfavorable subset of patients with locally advanced SCCHN it was not feasible. Future investigation of this novel treatment strategy utilizing modern angiographic catheter/microcatherter technology will involve a single dose of IA cisplatin with HFX-RT and dose intensification using neoadjuvant therapy.