Delayed wound healing in Mac-1–deficient mice is associated with normal monocyte recruitment

The Mac-1 integrin is an important mediator of migration and inflammatory activation of neutrophils and monocytes. However, the role of Mac-1 in modulating macrophage emigration and activation and its subsequent impact on cutaneous wound healing have not been fully elucidated. To examine the significance of Mac-1 to murine wound healing, we measured epithelialization and granulation tissue formation in partial-thickness ear wounds and full-thickness head wounds, respectively, in Mac-1-deficient mice. Wounds were histologically analyzed at postwounding days 3, 5, and 7. The gap measured between the leading edges of inward-migrating granulation tissue was significantly increased in knockout mice compared with control animals at day 5 (3.8+/-0.3 vs. 2.6+/-0.5 mm; p<0.001) and day 7 (2.2+/-0.4 vs. 0.96+/-0.73 mm; p=0.005). Epithelial gap measurements were also increased in knockout mice vs. wild-type controls at days 3 (0.62+/-0.02 vs. 0.54+/-0.07 mm; p<0.05) and 5 (0.58+/-0.06 vs. 0.39+/-0.08 mm; p<0.001). Immunohistochemistry showed equal numbers of macrophages in knockout and control wounds. These findings show that Mac-1 is required for normal wound healing but that the attenuation in the deposition of granulation tissue and wound epithelialization in Mac-1 knockout mice is not associated with decreased monocyte migration into the wound.     

Inhibition of bone healing by pamidronate in calvarial bony defects.

OBJECTIVE: Pamidronate has been studied as a therapeutic drug for various osteopenic diseases. However, avascular osteonecrosis in the jawbone has been recently reported in patients receiving pamidronate. The objective of this study was to examine the effect of pamidronate on bone regeneration in a controlled animal model. MATERIALS AND METHODS: To determine the effect of parmidronate on bone healing in a local bony defect area, a rabbit calvarial bony defect model was used and poly L-lactide-co-glycolide (PLGA) used as a drug carrier material. Four defect groups were made in each rabbit calvaria and the defects were treated as follows: untreated bony defect (group 1), PLGA only (group 2), 2 mg of pamidronate with PLGA (group 3), and 3 mg of pamidronate with PLGA (group 4). Bone healing was evaluated by radiography and histology at 1, 2, 4, 6, and 8 weeks after surgery. RESULTS: In radiographic analysis, radiopacity was lower in pamidronate groups than non-operated rabbit calvarial bone at all observation points (P < .05). In histological analysis, the initial bone formation at 1 week was not different among groups, but it was much lower in the pamidronate groups than in the control or PLGA group after 2 weeks. Newly formed bone at 1 week underwent avascular necrosis after 2 weeks in both pamidronate groups. Avascular necrosis was not observed until 8 weeks in both topically applied pamidronate groups. CONCLUSION: Collectively, pamidronate inhibits bone healing in rabbit calvarial bony defect and it may explain the avascular necrosis of the jaws in patients receiving pamidronate.     

Fracture risk in monoclonal gammopathy of undetermined significance.

To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7-fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined. INTRODUCTION: Multiple myeloma is often preceded by monoclonal gammopathy of undetermined significance (MGUS). Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover from excessive cytokine production. Whether fractures are also increased in MGUS is unknown. MATERIALS AND METHODS: In a population-based retrospective cohort study, 488 Olmsted County, MN, residents with MGUS first diagnosed in 1960-1994 (52% men; mean age, 71.4 +/- 12.8 years) were followed for 3901 person-years; follow-up was censored at progression to myeloma. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS AND CONCLUSIONS: Altogether, 200 patients experienced 385 fractures. Compared with expected rates in the community, statistically significant increases were seen for fractures at most axial sites, for example, vertebrae (SIR, 6.3; 95% CI, 5.2-7.5). There was a slight increase in hip (SIR, 1.6; 95% CI, 1.2-2.2) but not distal forearm fractures (SIR, 0.8; 95% CI, 0.4-1.5). The relative risk (SIR) of any axial fracture was 2.7 (95% CI, 2.3-3.1) compared with only 1.1 (95% CI, 0.9-1.4) for all limb fractures combined. In a multivariate analysis, the independent predictors of any subsequent fracture were age (hazard ratio [HR] per 10-year increase, 1.4; 95% CI, 1.2-1.6) and corticosteroid use (HR, 1.8; 95% CI, 1.2-2.6); greater weight at diagnosis (HR per 10 kg, 0.8; 95% CI, 0.8-0.9), and IgG monoclonal protein (HR, 0.7; 95% CI, 0.5-0.97) were protective. Baseline monoclonal protein level, a determinant of myeloma progression, did not predict fracture risk. Thus, the risk of axial, but not peripheral, fractures is increased among MGUS patients even before progression to myeloma. The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable.     

Topical Metronidazole Gel

Ten putrid-smelling decubitus ulcers were successfully treated with metronidazole gel. Anaerobes were cultured from five ulcers and Wood's light examination was positive in four ulcers before treatment. The odor was eliminated after 36 hours of therapy. All results of post-treatment cultures of anaerobes and Wood's light examinations were negative.     

MR characteristics of iophendylate (Pantopaque)

Although iophendylate (Pantopaque) has been largely replaced by water soluble agents for myelography, retained intracranial or intraspinal Pantopaque remains a common occurrence. Pantopaque has signal characteristics similar to fat with both short T1 and T2 relaxation times. In vitro measurements revealed T1 = 170 ms and T2 = 27 ms. Spine radiography is recommended in patients with a history of previous myelography and magnetic resonance abnormalities similar to fat.     

Simple Technique for Lip and Nasolabial Fold Anesthesia for Injectable Fillers

BACKGROUND: Minimally invasive cosmetic facial surgery procedures including injectable lip fillers are more popular than ever. Many of the newer fillers are more painful to inject than previous products and require a greater level of pain control. OBJECTIVE: The objective of this article is to describe a simple method of local anesthesia infiltration for pain control when injecting filler substances into the lips and perioral and nasolabial fold areas. MATERIALS AND METHODS: The preinjection topical anesthetic preparation, the actual infiltration techniques, and the author's experience are reviewed. RESULTS: These infiltration techniques are simple to perform and provide adequate anesthesia for the painless injection of filler substances in the lips and perioral, nasolabial regions. CONCLUSION: This simple intraoral infiltration technique is well tolerated and appreciated by patients and facilitates the experience of filler injection for both the patient and the doctor.     

Massive Immune Hemolysis Caused by Anti-D After Dual Kidney Transplantation

Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.     

Foot Polydactyly and Polysyndactyly: Genetic Implications in Two Families

The purpose of this study was to determine the genetic characteristics of foot polydactyly and identify its inheritance pattern by analyzing familial pedigree. Five cases from 2 Korean families were studied: 1 is a family whose members have been affected for 4 generations and the other for 2 generations. Using peripheral blood samples, we performed chromosomal analysis using the banding technique with Giemsa stain and karyotyping. We investigated the shape and structure of 46 chromosomes, looking for translation, deletion, inversion, ring chromosome, and isochromosome abnormalities. All peripheral blood samples demonstrated no chromosomal abnormalities, though the genetic nature of foot polydactyly and a new genetic locus was identified recently by other studies. Familial pedigree analysis suggested that polydactyly was inherited as an autosomal dominant trait in the first family. The mode of inheritance for the second family could not be determined due to an insufficient number of family members. The result of this study brought us to the conclusion that, while genetic factors play a major role in polydactyly, other factors may contribute to its occurrence.