Long-term safety assessment in children who received hydrolyzed protein formulas with Lactobacillus rhamnosus GG: a 5-year follow-up.

Extensively hydrolyzed (EH) formula with Lactobacillus rhamnosus GG (LGG) was demonstrated to alleviate cow's milk allergy (CMA) symptoms and promote faster acquisition of tolerance to cow's milk protein. We previously demonstrated that partially hydrolyzed (PH) and EH formulas with LGG supported normal growth in healthy-term infants through 120 days of age. The objective of the current study was to evaluate growth, development, and specific adverse events through 5 years of age in participants from that cohort who continued receiving study formula. Infants who completed a double-blind, randomized growth and tolerance study were eligible to continue receiving the assigned study formula through 1 year of age (control: EH casein formula, EHF, or one of two investigational formulas: EH casein formula with LGG (EHF-LGG) or a PH formula with LGG (PHF-LGG)) and participate in follow-up through 5 years of age. Anthropometric measures, behavior development, and specific adverse events were recorded. No significant differences in achieved weight and height or behavioral development outcomes at 3 or 5 years of age were observed among study groups. Few statistically significant differences in the incidence of specific infection-related events through years 3 or 5 were observed among study groups, none of which were considered clinically relevant. CONCLUSION: Extensively and partially hydrolyzed formulas with LGG were associated with normal growth and development and long-term safety through 5 years of age. What is Known: • Infants with cow's milk allergy often experience allergic manifestations that can lead to poor nutrition status and poor growth. • Providing partially hydrolyzed (PH) and EH formulas with or without LGG in infants can support normal growth in healthy-term infants. What is New: • This study provides long-term safety data for the first 5 years of life on the use of extensively and partially hydrolyzed formulas with LGG when fed through 1 year of age. • Extensively and partially hydrolyzed formulas with LGG are associated with normal growth, development, and long-term safety through 5 years of age.

Molecular analysis of a consortium of ruminal microbes that detoxify pyrrolizidine alkaloids.

Members of a consortium of bacteria, isolated from the rumen of sheep, that degrades pyrrolizidine alkaloids (PAs) found in tansy ragwort (Senecio jacobaea) were characterized. An enrichment of ruminal bacteria was isolated from a sample of ruminal fluid using standard anaerobic techniques. The PA degradative capacity of the enrichment was tested by spiking purified PA extract from tansy ragwort. Length heterogeneity analysis by PCR (LH-PCR) and restriction fragment length polymorphism (RFLP) analysis was used to identify members of the consortium. Phylogenetic analysis of the 16S rDNA gene revealed differing results based on the molecular method used. LH-PCR identified 7 different organisms in 3 groups while RFLP identified 6 organisms with differing banding patterns in 5 groups. After the phylogenetic analyses of both methods were combined, the combined isolates represented 6 groups. The majority of the members of this consortium are <97.0% homologous with known bacteria, indicating this consortium may contain novel organisms able to detoxify PAs found in tansy ragwort. Further understanding of the metabolic pathways used by this consortium to degrade PAs could lead to the use of the consortium as a probiotic therapy for livestock and horses afflicted with tansy ragwort toxicosis.

Antimicrobial activity of some Pacific Northwest woods against anaerobic bacteria and yeast.

Extracts of woods commonly used for animal bedding were tested for antimicrobial activity. Essential oils from Alaska cedar (Chamaecyparis nootkatensis), western juniper (Juniperus occidentalis) and old growth Douglas fir (Pseudotsuga menziesii) as well as methanol extracts of wood from these trees plus western red cedar (Thuja plicata) and ponderosa pine (Pinus ponderosa) were tested for antimicrobial activity against anaerobic bacteria and yeast. The test microbes included Fusobacterium necrophorum, Clostridium perfringens, Actinomyces bovis and Candida albicans which are common to foot diseases and other infections in animals. The essential oils and methanol extracts were tested using a standardized broth assay. Only extracts of Alaska cedar and western juniper showed significant antimicrobial activity against each of the microbes tested. The essential oil of Douglas fir did show antimicrobial activity against A. bovis at the concentrations tested. The methanol extracts of the heartwood of Douglas fir and the sapwood of ponderosa pine showed no antimicrobial activity. The major chemical components of western juniper (cedrol and alpha- and beta-cedrene) and Alaska cedar (nootkatin) were also tested. In western juniper, alpha- and beta-cedrene were found to be active components. Nootkatin showed activity only against C. albicans. The inhibitory activity in Alaska cedar oil was high enough to justify further efforts to define the other chemical components responsible for the antimicrobial activity.

Rosette-forming non-Hodgkin's lymphomas.

Homer Wright rosettes, typically found in neuroblastomas and consisting of neoplastic cells surrounding an eosinophilic fibrillary centre without a lumen, have been considered as an important finding in the differential diagnosis of small round cell tumours. Rosettes in a neoplasm involving lymph nodes or bone marrow traditionally excluded a diagnosis of malignant lymphoma. In this report, we describe three cases of malignant lymphoma (two small lymphocytic and one diffuse large cell) with pronounced rosette formation. One of the two cases of small lymphocytic lymphoma was observed in the bone marrow, the other small lymphocytic lymphoma and the large cell lymphoma were in lymph nodes. The rosettes consisted of neoplastic lymphoid cells, often with participation of reactive macrophages, and ultrastructurally they had a central mass of interdigitating fibrillary cytoplasmic projections. Two cases were of B-cell lineage and one was of T-cell lineage. To the best of our knowledge, this is the first report of T-cell lymphoma with rosettes. Based on these findings, it is suggested that non-Hodgkin's lymphoma be included in the differential diagnosis of rosette-forming round cell neoplasms.

The progressive outer retinal necrosis syndrome. A variant of necrotizing herpetic retinopathy in patients with AIDS.

BACKGROUND: The progressive outer retinal necrosis syndrome is a recently recognized variant of necrotizing herpetic retinopathy. This report characterizes more fully its clinical features and course. METHODS: Using standardized clinical criteria, patients with progressive outer retinal necrosis syndrome from four institutions were identified. Patient records were reviewed retrospectively for the following data: medical and demographic characteristics, presenting symptoms, physical findings, course, responses to treatment, and outcomes. RESULTS: Thirty-eight patients (65 involved eyes) were studied. All had acquired immune deficiency syndrome. A known history of cutaneous zoster was documented in 22 (67%) of 33 patients. Median CD4 lymphocyte count was 21/mm3 (range, 0-130/mm3). Median follow-up was 12 weeks. The most common presenting symptom was unilateral decreased vision (35 of 65 eyes, 54%); median visual acuity at presentation was 20/30 (range, 20/20 to no light perception [NLP]). Anterior chamber and vitreous inflammatory reactions were absent or minimal in all patients. Typical retinal lesions were multifocal, deep opacities scattered throughout the periphery, although macular lesions also were present in 21 eyes (32%) at diagnosis. Lesions progressed rapidly to confluence. Initial intravenous antiviral therapy appeared to reduce disease activity in 17 (53%) of 32 eyes, but treatment did not alter final visual outcome. Visual acuity was NLP in 42 (67%) of 63 eyes within 4 weeks after diagnosis. Retinal detachment occurred in 43 (70%) of 61 eyes, including 13 (93%) of 14 eyes that received prophylactic laser retinopexy. CONCLUSION: The progressive outer retinal necrosis syndrome is characterized by features that distinguish it from cytomegalovirus retinopathy, acute retinal necrosis syndrome, and other necrotizing herpetic retinopathies. Visual prognosis is poor with current therapies.

Ocular toxoplasmosis misdiagnosed as cytomegalovirus retinopathy in immunocompromised patients.

BACKGROUND: Cytomegalovirus (CMV) and Toxoplasma gondii both cause necrotizing retinopathy in immunosuppressed hosts. Because of the high prevalence of serum antibodies to these agents in the general population and the risks associated with retinal biopsies, diagnosis of these infections is usually based on clinical findings alone, but the two infections can be confused with one another because of similar clinical features. Accurate diagnosis is critical, however, because both diseases are treatable but require different medical therapies. METHODS: Case histories were reviewed for five immunosuppressed patients with necrotizing retinopathy, which was initially diagnosed incorrectly as CMV retinopathy but was subsequently found to be toxoplasmic retinochoroiditis. Correct diagnosis was based on retinal biopsy (2 cases) or rapid response to antiparasitic drug therapy (3 cases). Factors were sought that might help differentiate toxoplasmic retinochoroiditis from CMV retinopathy at presentation. RESULTS: In all cases, the character of retinal opacification (densely opaque, thick) and the appearance of lesion borders (smooth, nongranular) was different from that typically seen with CMV retinopathy. These cases also were characterized by prominent anterior chamber and vitreous inflammatory reactions (four of five cases) and relative lack of retinal hemorrhage. One patient subsequently developed CMV retinopathy; characteristics of the two lesions in the same eye highlighted the differences between these two infections. CONCLUSION: Clinicians should consider ocular toxoplasmosis as a cause of necrotizing retinopathy in immunosuppressed patients and consider an empiric course of antiparasitic therapy for lesions with features described in this report.

Recurrence of presumed varicella-zoster virus retinopathy in patients with acquired immunodeficiency syndrome.

Five patients with acquired immunodeficiency syndrome (AIDS) and presumed varicella-zoster virus retinopathy had recurrence of retinopathy after stabilization with initial intravenous antiviral therapy. Recurrences were recognized as increased retinal opacification at the borders of preexisting lesions or as new lesions. In four of the five patients, recurrences were temporally associated with a reduction in the amount of antiviral medication being received. Changes included switch from intravenous to oral acyclovir (two patients), taper of oral acyclovir (one patient), and discontinuation of medications (one patient). In four patients disease was initially unilateral; in three of these four, disease subsequently developed in the previously unaffected fellow eye at the time of recurrence. The median time from stabilization of disease to recurrence was 51 days (range, 14 to 90 days). In contrast to the management of varicella-zoster virus retinopathy in immunocompetent patients and varicella-zoster virus lesions of the skin, varicella-zoster virus retinopathy in patients with AIDS appears to require chronic suppressive antiviral therapy to prevent recurrences. In this respect it is similar to other opportunistic retinal infections in patients with AIDS. The best drugs and optimal treatment regimens for maintenance antiviral therapy remain unknown.

Localized recurrent postoperative pernio associated with leukocytoclastic vasculitis.

A patient with recurrent pernio of the right ankle for 21 years after surgery had a leukocytoclastic vasculitis localized in the area. We suggest that the various histologic descriptions of pernio in the literature and in this case represent different levels of severity of the disease.

Serous adenocarcinoma of the uterus metastatic to the urinary bladder mimicking primary bladder neoplasia. A report of a case.

A 72-year-old woman with a history of transitional cell carcinoma of the urinary bladder was found to have a vesical neoplasm at cystoscopy. Microscopic examination of a biopsy specimen showed papillary adenocarcinoma. A subsequent endometrial biopsy, performed because of vaginal spotting, disclosed a serous papillary adenocarcinoma. A hysterectomy was performed. Pathologic examination showed that the tumor was deeply invasive of the myometrium. The uterine and bladder tumors were similar histologically. This case suggests that when examining a pure adenocarcinoma of the bladder, the pathologist should consider the possibility that it represents metastatic disease even in the absence of a known tumor elsewhere.

A controlled and blinded study of immunoreactant deposition at the dermal-epidermal junction of patients with primary fibrositis syndrome.

The prevalence of immunoreactant deposition at the dermal-epidermal junction (DEJ) in clinically normal, sun exposed skin was assessed by direct immunofluorescence (IF) in 36 patients with primary fibrositis syndrome (PFS) and 12 clinically healthy control subjects. A granular or homogeneous deposition of IgG was seen at the DEJ in 52.8% (19/36) of patients with PFS and in 16.7% (2/12) of controls. The difference in IgG deposition between patients with PFS and controls was statistically significant (p = 0.030). Patients with PFS and controls did not demonstrate significant IF staining for IgA, IgM, or C3. Albumin deposition at the DEJ appeared to parallel IgG deposition in patients with PFS and control subjects who were positive for this immunoglobulin. No relationship was noted between IgG deposition and demographic or clinical characteristics of these patients' disease. These data suggest that IgG and albumin deposition at the DEJ is frequent in PFS and that further study of this skin phenomenon is warranted.

Intraoral solitary glomus tumor (glomangioma): case report and literature review.

The glomus tumor, or glomangioma, is a benign neoplasm arising from the normal glomus. Glomus tumors of the oral cavity are rare, with only ten cases reported in the literature. We report the light and electron microscopic features of an additional case of glomus tumor of the lip which occurred as a solitary, painless, submucosal mass in a 51-year-old woman. Clinical, diagnostic, and histogenetic aspects are discussed.

Pigmented villonodular synovitis of synovial joints: clinical, pathologic, and radiologic features.

The clinical, pathologic, and radiologic features of pigmented villonodular synovitis of large synovial joints are presented. The typical plain-film presentation of this unusual entity is a noncalcified capsular soft-tissue mass of the knee, without bony abnormalities. When pigmented villonodular synovitis occurs in other joints, it is often accompanied by cystic bone erosions. This important radiographic finding might mislead one to an improper diagnosis of neoplasia or infection. This review reveals insufficient emphasis in the radiologic literature on the high incidence of bone lesions in joints affected by pigmented villonodular synovitis. A mechanism for the development of bone cysts is proposed. Clinical, pathologic, radiologic, and therapeutic considerations are discussed.

Primary adenomatous neoplasms of the middle ear: light and electron microscopic features of a group distinct from the ceruminomas.

The light and electron microscopic features of two primary adenomatous neoplasms of the middle ear are presented and compared with those cases in the literature. Primary adenomatous neoplasms of the middle ear appear to be derived from the lining epithelium of the middle ear and are distinct from the cercuminomas. They exhibit benign or indolently malignant behavior. Cytologic and histologic features are bland and uniform. Invasion of adjacent soft tissues and/or bone is the only histologic feature indicative of malignancy. Distant metastasis has not been reported. The duration and nature of the symptoms are of little diagnostic value. Radiographic and/or operative evidence of bone erosion reflects the aggressive potential of these neoplasms, although its absence does not exclude microscopic invasion. The primary adenomatous neoplasms of the middle ear recur locally if incompletely excised. Radical mastoidectomies and/or complete removal through the external auditory canal are curative.

Chronic interstitial nephritis. Its occurrence with oxalosis and anti-tubular basement membrane antibodies after jejunoileal bypass.

A 38-year-old woman suffered rapid onset of renal failure between 11 and 15 months after undergoing a jejunoileal bypass for morbid obesity. Microscopic examination of renal biopsy specimens revealed oxalosis and severe tubulointerstitial nephritis. Immunofluorescence microscopy disclosed linear staining of tubular basement membranes with antisera to IgG and C3, which suggests antitubular basement membrane disease, a side effect not previously recognized with jejunoileal bypass. Possible mechanisms leading to the formation of these antibodies include (1) oxalate damage to renal tubules with release of tubular basement membrane antigens, and (2) bacterial overgrowth in the bypass segment, with mucosal damage and release of intestinal mucosal antigens that share antigenetic determinants with renal proximal tubules. Anti-tubular basement membrane disease may be an additional mechanism that produces or enhances renal damage in patients with jejunoileal bypass.

Recurrent systemic lupus erythematosus involving renal allografts.

Two cases of recurrent lupus erythematosus involving renal transplants are described. Neither case showed changes of transplant rejection. The clinical course, serologic tests, and renal histopathologic findings remarkably paralleled those seen during each patient's primary disease presentation. Typical and severe extrarenal manifestations of dermatitis, pleuritis, and polyarthritis were noted before renal allograft lupus involvement. Rapid renofunctional deterioration was halted in one patient by plasmapharesis. In the second patient a more protracted course involving the allograft is anticipated. Although previous experiences suggest that lupus disease activity "burns out" after the development of chronic renal failure, findings from these two cases argue against this presumption. Longer periods of transplant follow-up may show more recurrence of lupus erythematosus.

Estrogen receptors in male breast cancer: clinical and pathologic correlations.

Breast cancer tissue from 12 male patients was evaluated for the presence of estrogen receptors (ER), and at least 10 of 12 were found to be high in ER (ER+). A combination of previously published cases and our own experience indicates that 80% of patients (37/47) have ER+ tumors. This incidence of ER positivity in men is greater than that in women with breast cancer. Clinical responses to hormonal therapy have been observed in the ER+ patients but not in one ER--patient. Measurement of ER may be clinically important in men with breast cancer.

Carcinoma of the larynx in childhood.

The unusual case of a 12-year-old boy with well differentiated in situ, and focally invasive squamous carcinoma of the larynx is reported, together with a review of the medical literature. In addition to this one, 54 cases of laryngeal carcinoma in children 15 years of age or younger have been reported since 1868. All were squamous except for one adenocarcinoma of a laryngeal minor salivary gland. Carcinoma of the larynx in children parallels that of adults in terms of squamous histology, predominantly vocal cord involvement, pattern of local spread, and response to treatment. However, the incidence of female patients is higher in childhood (40% of childhood cases vs. less than 10% of adult cases), and risk factors, except previous irradiation of papillomas, are rare. Although unusual, carcinoma of the larynx in children is probably more common than thought and the diagnosis should be considered in any case of a child with persistent hoarseness or cough.

Atypical pseudoepitheliomatous hyperplasia and squamous cell carcinoma in chronic cutaneous sinuses and fistulas.

Three cases are presented in which changes of atypical pseudoepitheliomatous hyperplasia (APH) occurred in chronically draining cutaneous sinuses and fistulas. In two of the cases, unequivocal squamous cell carcinoma developed. Because the term APH fails to convey adequately to the surgeon the essentially malignant nature of this process and the need for aggressive treatment, we feel that the term should be discarded. Based on our cases and those reported in the literature, it is our opinion that, in the presence of soft-tissue and bony invasion, a diagnosis of well-differentiated squamous cell carcinoma is appropriate even in the absence of unequivocal cellular changes of malignancy.