Limb body-wall complex in association with sirenomelia sequence.

Limb body-wall complex and sirenomelia sequence are uncommon birth defects and their association is extremely rare. Their overlapping manifestations and their concurrence in our patient suggest that they share a common cause and belong to a group of pathologically closely related conditions. Embryonic vascular disruption may be a common pathogenesis in both anomalies.

Periorbital infantile myofibromatosis.

An 11-day-old boy was found to have a lesion of the left lower eyelid and medial canthus. The mass was present at birth and subsequently enlarged, and was subtotally excised when the child was 2 months old. Histopathologic examination disclosed a fascicular to slightly nodular pattern of predominantly spindle-shaped cells. Special stains demonstrated fibroblastic and smooth-muscle features in individual cells, and infantile myofibromatosis was diagnosed. Sixteen months postoperatively, no evidence of recurrence was noted. We believe this is the first case of infantile myofibromatosis of the solitary type involving the ocular adnexa of a neonate to be reported in the English literature. Infantile myofibromatosis of the solitary type appears to have an excellent prognosis and may be treated with conservative resection if the tumor infiltrates important adnexal structures.

The role of photodynamic therapy in posterior fossa brain tumors. A preclinical study in a canine glioma model.

Photodynamic therapy was studied in dogs with and without posterior fossa glioblastomas. This mode of therapy consisted of intravenous administration of Photofrin-II at doses ranging from 0.75 to 4 mg/kg 24 hours prior to laser light irradiation in the posterior fossa. Tissue levels of Photofrin-II were four times greater in the tumor than in the surrounding normal brain. Irradiation was performed using 1 hour of 500 mW laser light at a wavelength of 630 nm delivered through a fiberoptic catheter directly into the tumor bed via a burr hole. All animals receiving a high dose (4 or 2 mg/kg) of Photofrin-II developed serious brain-stem neurotoxicity resulting in death or significant residual neurological deficits. A lower dose (0.75 mg/kg) of Photofrin-II produced tumor kill without significant permanent brain-stem toxicity in either the control animals or the animals with cerebellar brain tumors receiving photodynamic therapy.

Prevention of gallium toxicity by hyperhydration in treatment of medulloblastoma.

In vitro and in vivo studies have established gallium nitrate as an effective chemotherapeutic agent against human medulloblastoma. In vitro, gallium nitrate reduced cell proliferation and DNA synthesis of medulloblastoma Daoy. Gallium inhibits the availability of 59Fe to ribonucleotide reductase and has a direct effect on the enzyme itself. In vivo, gallium demonstrated similar effects on the medulloblastoma Daoy cell line in nude mice. Tumor growth rate and actual size were decreased; however, severe nephrotoxicity and mortality were observed. In our study, intradermal injections of medulloblastoma Daoy cells were given to nude mice and then tumors were allowed to grow. Tumor-bearing mice received a 15-day gallium (50 mg/kg/day) regimen, 20-day rest, 7-day gallium (66.5 mg/kg/day) dose escalation regimen beginning when tumor size exceeded 8-10 mm in diameter. All treated and control mice received saline hyperhydration during both treatment sessions. Our study resulted in the prevention of severe toxicity and an inhibition of tumor growth. No toxicity occurred with gallium nitrate at 50 mg/kg/day. Severe morbidity and mortality were observed at the higher gallium dose level (66.5 mg/kg/day), suggesting that the 50 mg/kg/day dose is the appropriate level when investigating gallium nitrate as a chemotherapy agent in nude mice.

Antineoplastic effects of gallium nitrate on human medulloblastoma in vivo.

Gallium nitrate possesses antineoplastic activity against certain solid tumors and has been demonstrated to be an effective agent in reducing cell proliferation and DNA synthesis in the medulloblastoma Daoy cell line in vitro. In prior studies, gallium inhibited the cellular uptake of 59Fe by brain tumor cells; however, this block in 59Fe uptake was variable and closely paralleled the inhibitory effects of gallium on cell growth. In vivo trials now have been conducted and have yielded some promising results. Nude mice received intradermal injections of medulloblastoma Daoy and then allowed to grow tumors. When the mice had developed at least one tumor between 9 to 10 mm in diameter, a 10-day course of intraperitoneal gallium nitrate injections was initiated. Gallium nitrate treatment reduced overall tumor growth rate and reduced actual tumor size. Nephrotoxicity was severe, but may be preventable by continuous gallium infusion and use of diuretics and hyperhydration.

Congenital Volkmann ischaemic contracture: a case report and review.

Congenital Volkmann ischaemic contracture or neonatal compartment syndrome has rarely been discussed in the literature of dermatology. The condition often involves the upper extremity with cutaneous lesions, contractures and neuropathy. Because the lesions can be mistaken for other entities including necrotizing fasciitis, neonatal gangrene, congenital varicella, aplasia cutis congenita, amniotic band syndrome, subcutaneous fat necrosis and epidermolysis bullosa, dermatologists play a significant role in the diagnosis and, consequently, the treatment of the patient. We describe a premature newborn who had a unilateral, well-demarcated necrotic plaque with a central pallor at birth. The plaque extended circumferentially over the left forearm from the wrist to the elbow. Left wrist oedema, bullae over the fingers and flaccid paralysis at the wrist were also noted.

Anesthesia-induced rhabdomyolysis in infants with unsuspected Duchenne dystrophy.

Anesthesia-induced rhabdomyolysis in infancy may represent an unsuspected Duchenne dystrophy. In order to establish the diagnosis of this genetic disease more definitively, a dystrophin test is a requisite following the conventional creatine kinase test and light and electron microscopies of the muscle biopsy.

Cutaneous mucinosis of infancy.

Cutaneous mucinosis of infancy has been reported only rarely in the literature. We describe a case occurring in a black infant girl. Although no associated abnormalities have been described previously, our patient had a history of developmental delay, congenital cataracts, bilateral inguinal hernias, and an accessory tragus. The significance of these features is unclear.

Acrally occurring dermatofibrosarcoma protuberans in children and adults.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) arising on the hands and feet is unusual and, at any site, is extremely rare in children. OBJECTIVE: We report a 5-year-old girl who developed DFSP on her hand at 9 months of age. We review the clinical features and treatment of childhood DFSP and of acrally occurring DFSP at all ages. CONCLUSION: DFSP in children develops most often on the back (22.2%) and at acral sites (14.8%). It occurs on the hands and feet of children more commonly than in adults. This may be related to the increased frequency of trauma at these sites in children. Mohs micrographic surgery is the treatment of choice for DFSP.

Dermatomal lichenoid chronic graft-vs-host disease following varicella-zoster infection despite absence of viral genome.

Localized cutaneous graft-versus-host disease (GVHD) following a dermatomal distribution or in a pattern of Blaschko's lines. Some authors have postulated that dermatomal GVHD is triggered by a varicella-zoster virus infection, although in reported cases, there was no history of a preceding herpes zoster. We describe a case of GVHD localized to the exact dermatome of a culture-proven varicella-zoster virus infection. PCR analysis failed to detect persistence of viral genome in the affected skin.

Renal transplantation in a child with primary oxalosis.

Primary hyperoxaluria (oxalosis) is an autosomal recessive disorder due to an inherited deficiency of the peroxisomal alanine:glyoxylate aminotransferase characterized by increased production and urinary excretion of oxalate and glycolate resulting in renal failure due to oxalate deposition. Because of the risk of continuing oxalate deposition in the transplanted kidney, oxalosis had been considered a contraindication for transplantation. A 5-year-old boy with oxalosis, maintained on peritoneal dialysis, received a haploidentical qiving-related transplant. The preoperative management included donor-specific transfusions and daily hemodialysis to remove a maximum amount of oxalate. The immunosuppression consisted of azathioprine and prednisone. Aggressive fluid management including noncalciuric diuretics (hydrochlorothiazide) kept urine output high. Pyridoxine, magnesium, neutral phosphate and sodium benzoate were used to prevent deposition of oxalate in the transplanted kidney. Two acute rejection episodes responded to steroid boluses. A kidney biopsy during the second rejection episode confirmed the diagnosis but also revealed oxalate deposits in the transplanted kidney. More than 4 years after transplantation, the patient has catch-up growth and his serum creatinine is 1.4 mg/dl. In conclusion, oxalosis is not an absolute contraindication to renal transplantation. Transplantation can be performed successfully utilizing living-related donor kidneys and aggressive medical management. The risks of deterioration of function and oxalate deposition in the transplant kidney are offset by improvement in quality of life.

Infiltrating T cells during liver graft-versus-host disease show a restricted T-cell repertoire.

Data from animal models have shown that hepatic graft-versus-host disease (GVHD) may be mediated by donor T cells interacting with liver adhesion molecules, other minor histocompatibility antigens, or both. We hypothesized that T-cell infiltrates within a liver biopsy during clinical GVHD would show a restricted T-cell response because the T cells would be responding to a limited number of antigens. We studied the peripheral T-cell repertoire and the liver-infiltrating T-cell repertoire of a patient who developed skin GVHD and subsequent liver GVHD after a matched sibling bone marrow transplantation for acute myeloid leukemia. Spectratype analysis of peripheral blood at the time of liver GVHD revealed that the patient had reconstituted a complex peripheral T-cell repertoire as evidenced by the presence of complementarity-determining region 3 (CDR3) length heterogeneity in most of the T-cell families. The repertoire complexity was skewed in variable gene beta (VB) 5.3, VB4, VB7, VB8, and VB15. Spectratype analysis on the liver biopsy sample revealed a limited infiltrate with an oligoclonal expansion in VBs 4, 7, and 8. We evaluated the T-cell infiltrate in more detail by sequencing the relevant expansions noted by spectratype and developing probes for the predominant CDR3 sequences. These clonotype probes were hybridized to peripheral blood and liver samples from the patient, a T-cell line developed from the patient's peripheral blood at the time of the initial skin GVHD, the donor's blood and marrow, and control samples. The results showed that the T-cell infiltrate during liver GVHD is mediated by a limited number of T cells, and that those cells are mostly different from the ones expanded from the peripheral blood during an acute skin GVHD reaction. These data support the concept that liver GVHD is a response to tissue-specific minor histocompatibility antigens.

Neonatal hypotonia and cardiomyopathy secondary to type IV glycogenosis.

A neonate with deficiency of branching enzyme (glycogenosis type IV) presented symptoms of severe hypotonia pre- and postnatally, and dilated cardiomyopathy in early infancy. The classical clinical manifestation of liver cirrhosis was not present, although amylopectin-like inclusions were found in the hepatocytes. In contrast to a previous report, the neurons in the brain stem and spinal anterior horns contained PAS-positive, diastase-resistant deposits. The combined involvement of the muscles and motor neurones could account for the severity of hypotonia. The muscle biopsy, electromyogram and biochemical and enzyme assays were helpful in establishing the diagnosis.

Inflammatory myofibrohistiocytic proliferation simulating sarcoma in children.

The term "inflammatory myofibrohistiocytic proliferation" (IMP) has been proposed to replace the conventional designations of plasma cell granuloma and inflammatory pseudotumor. Three cases of extrapulmonary IMP in children are reported, including an intracerebral lesion which has been formerly undescribed. In children, IMP may be associated with microcytic hypochromic anemia, hypergammaglobulinemia, and high erythrocyte sedimentation rate. In this clinical setting, differentiation of a rapidly growing but benign IMP from a bona fide sarcoma is of paramount importance.

Selective incorporation of 111In-labeled PHOTOFRIN by glioma tissue in vivo.

The use of PHOTOFRIN for photodynamic therapy of human gliomas has been studied by i.v. administration and laser photosensitization. Defining the uptake of PHOTOFRIN in the patient's tumor in comparison with the surrounding normal brain tissue is highly desirable for patient selection and study of in vivo kinetics. We utilized a non-invasive approach to the detection of PHOTOFRIN uptake in brain tumors with 111In-oxine radiolabeled PHOTOFRIN and external imaging and quantitation using a gamma camera. Biodistribution of 111In-labeled PHOTOFRIN in 13 organs was determined in four dogs and 15 mice with gliomas. 99mTc-DTPA was used as a control for nonspecific uptake. The greatest concentration of 111In-PHOTOFRIN in the brain tumor occurred at 24 hours post i.v. administration. The brain tumor PHOTOFRIN uptake was seven times greater than that of normal brain. The decreased blood background at 72 hours made this the optimum time for imaging. Specific tumor tissue uptake of 111In-PHOTOFRIN occurred, well beyond that resulting from blood-brain-barrier (BBB) breakdown.