Protein restriction in chronic renal failure

The aim of the study was to investigate the effect of a protein restricted diet on renal function and growth of children with chronic renal failure. In a multicentre prospective study 56 children (aged 2-18 years) with chronic renal failure were randomly assigned to the protein restricted (0.8-1.1 g/kg/day) or the control group. All children were followed up by the same paediatrician and dietitian. After a follow up period of three years there was no significant difference in glomerular filtration rate between children on a protein restricted diet and children of the control group. There was no significant difference in weight with respect to height and height SD score between the protein restricted and the control group. Compliance with the protein restricted diet, as indicated by the prospective diet diaries and the serum urea:creatinine ratio, was good. This study shows that children with chronic renal failure do not benefit from a protein restricted diet.     

A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy

We performed a phase I trial of recombinant human interleukin-11 (rhIL- 11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model.     

Histologic reactions to cutaneous infections by Mycobacterium haemophilum.

Mycobacterium haemophilum is an emerging pathogen in immunocompromised patients. We report the clinical and histologic findings of 16 skin biopsies from 11 patients with culture-proven infections by M. haemophilum. The patients had leukemia or non-Hodgkin's lymphoma. Ten of them had undergone bone marrow transplantation. When the skin biopsy specimens were taken, a portion of the skin was simultaneously submitted to a microbiology laboratory for cultures. The remaining skin was processed routinely. Acid-fast bacilli were found in 11 of 16 lesions. The number of histologically detectable organisms was typically low: nine biopsies had fewer than three bacilli per 50 oil immersion fields. The most common histologic pattern was a mixed suppurative and granulomatous reaction (7 of 16 biopsies). Four biopsies showed well-formed epithelioid granulomas. Two showed necrosis, one of which was ulcerated. One lesion was a subcutaneous abscess. Two biopsies showed a mixed lichenoid and granulomatous dermatitis. In one of them, the granulomatous reaction was focal and small. One biopsy lacked a granulomatous tissue reaction altogether; it showed an interface dermatitis, a perivascular and periadnexal lymphocytic infiltrate, and necrotizing lymphocytic small vessel vasculitis. A subsequent biopsy from the same patient additionally showed a focal granulomatous reaction. Our observation that infections by M. haemophilum can present with nongranulomatous or pauci-granulomatous reactions without necrosis is of note. Failure to suspect mycobacterial infection in such reactions contributes to probable underreporting of M. haemophilum and to misdiagnoses. Furthermore, our findings emphasize the importance of simultaneous biopsies for culture and histology in immunocompromised patients.     

Multiple lesions of granular cell basal cell carcinoma: a case report

Granular cell change in basal cell carcinoma (BCC) occurs rarely. Only 11 such cases have been reported; all of them were solitary nodular BCC. We report herein a case of multiple granular cell BCC with infundibulocystic features. The tumors presented as papules on the anterior neck of a 44‐year‐old female with a prior history of a well‐differentiated squamous cell carcinoma (SCC) of the tongue and radiation involving the area in which BCC developed. Microscopically, the tumors were circumscribed small dermal nodules composed of epithelial cords with granular eosinophilic cytoplasm and entrapped infundibular keratocysts. Given the eosinophilic appearance of the tumor, history of SCC and the lesions multiplicity, the initial biopsy was first interpreted as metastatic SCC. The correct diagnosis of granular cell BCC was established upon rereview of the slides at a cancer center. Given the diagnostic controversy, immunohistochemical stains were performed. The tumor cells expressed Ber‐EP4, CD63 (NKI/C3) and CD68. The tumors were compared to the prior SCC finding different morphologies. Extensive clinical evaluation showed no evidence of recurrent SCC. This report expands the clinicopathologic spectrum of granular cell variant of BCC and documents for the first time eruption of multiple such tumors in a localized area.     

Interleukin-6 release by rat liver macrophages

Tissue macrophages of the liver (Kupffer cells) release interleukin-6 (IL-6) in vitro. Since Kupffer cells reside in close proximity to hepatocytes, which are major target cells of IL-6, the regulation of IL-6 release by hepatic macrophages has been investigated in this study. Using the hybridoma growth test to detect IL-6, we found that Kupffer cells already maximally release IL-6 at endotoxin concentrations as low as 1.0 ng/ml. The stimulated secretion of IL-6 was increased 4-8-fold by endotoxin when compared to the control macrophages incubated in serum-containing medium alone. The preincubation of macrophages with interferon-gamma enhanced the capacity of Kupffer cells to respond to endotoxin. The secretion of IL-6 could also be induced by interleukin (IL)-1 beta and tumor necrosis factor (TNF-alpha). The most potent inducers, however, were the paramyxoviruses Newcastle Disease Virus and Sendai Virus. The release of IL-6 by macrophages upon stimulation with endotoxin was almost completely inhibited by 1 microM dexamethasone. Whereas 100 nM of prostaglandin E2 (PGE2) inhibited the release of TNF-alpha in rat Kupffer cells, it did not affect the secretion of IL-6.