Dental panoramic radiographic evaluation in bisphosphonate-associated osteonecrosis of the jaws

Objectives:  To determine the extent to which clinical and radiographic features of bisphosphonate-associated osteonecrosis of the jaw (BONJ) are correlated.
Design:  Retrospective case review.
Methods:  The records of 39 patients diagnosed with BONJ and examined by panoramic radiography were retrospectively evaluated. The arches were divided into sextants ( n  = 234) and evaluated for the following signs: sclerosis, surface irregularity, sockets, fragmentation and lysis.
Main outcome measures:  The McNemar, Kruskall–Wallis and equivalency tests were performed to analyze the association between clinical and radiographic signs and BONJ severity.
Results:  Sixty-two out of 234 sextants were abnormal by clinical criteria and 61 out of 234 sextants demonstrated at least one radiographic abnormality. There was agreement between clinical and radiographic detection in 41 sextants. The data showed equivalency between BONJ diagnosis and both sclerosis and surface irregularity. The correlation between number of clinical sites and any radiographic finding was significant in the maxilla ( P  < 0.001) but not in the mandible ( P  = 0.178). The total number of radiographic signs per patient increased with BONJ stage.
Conclusion:  Focal panoramic radiographic findings of sclerosis and surface irregularity correlate with clinical sites of BONJ. This may be a useful and reliable tool to detect early changes of BONJ or to confirm a clinical diagnosis.     

Simvastatin and losartan enhance nitric oxide and reduce oxidative stress in salt-induced hypertension

BACKGROUND: The renin-angiotensin-aldosterone system and oxidative stress play a major role in the pathogenesis of hypertension. METHODS: We examined the effects of simvastatin, an HMG-CoA inhibitor, and losartan, an angiotensin type 1 receptor antagonist, in Dahl rats fed a high salt diet (8% NaCl), and treated with either simvastatin (3 mg/kg/d), losartan (10 mg/kg/d), or their combination using the drinking water as vehicle, for 3 weeks. Mean blood pressure (MAP) was measured by tail-cuff plethysmography. Plasma levels of nitric oxide (NO) and prostanoids, as well as plasma and tissue angiotensin II (Ang II) and aldosterone (ALDO) were analyzed by enzyme immunoassay. Renal and aortic superoxide production was determined by fluorescence spectrometry. Vascular reactivity of second-order mesenteric arteries was assessed in vitro. RESULTS: Simvastatin, losartan, and the drug combination attenuated the salt-induced increase in MAP. Plasma NO was elevated by simvastatin, losartan, and the combination, whereas plasma thromboxane was reduced by losartan. Simvastatin, losartan, and the combination reduced renal Ang II, but only the combination reduced cardiac Ang II. Heart and renal ALDO were reduced by simvastatin, losartan, and the combination. Aortic and renal NADPH-dependent superoxide production was reduced by simvastatin, losartan, and the combination. The response to acetylcholine, in mesenteric arteries preconstricted with norepinephrine, was greater in the losartan group. CONCLUSIONS: Thus, treatment with simvastatin and losartan lowered oxidative stress and improved endothelial function. Simvastatin significantly reduced the effect of losartan on vascular reactivity in mesenteric arteries, suggesting that their combination may be contraindicated.     

Prostacyclin Reversal of Lethal Endotoxemia in Dogs

Severe endotoxemia, a condition where microembolization and intravascular coagulation are thought to play important roles, was treated experimentally with prostacyclin (PGI₂). In a study of 24 dogs, 8 control animals injected with 1.75 mg·kg⁻¹ of endotoxin died within 24 h. Six animals given intravenous aspirin 100 mg/kg, 30 min after endotoxin died. 9 of 10 dogs infused with 100 ng PGI₂·kg⁻¹·min⁻¹ for 3 h, given 30 min after the injection of endotoxin survived 24 h (P < 0.025). Injection of endotoxin resulted in a: (a) maximal 62% fall in mean arterial pressure (P < 0.001); (b) transient doubling of mean pulmonary arterial pressure (P < 0.001); (c) initial 70% drop in cardiac index (P < 0.001); (d) decline in blood platelets from 213,700 to 13,700/mm³ (P < 0.001), and leukocytes from 7,719 to < 750/mm³ (P < 0.001); (e) depressed urine output (P < 0.001); (f) 34% decrease in blood fibrinogen (P < 0.01) and an increase in fibrin degradation products > 50 μg/ml (P < 0.001); (g) fivefold increase in circulating cathepsin D titer (P < 0.005) and (h) increase in blood norepinephrine (P < 0.005), dopamine (P < 0.005), and epinephrine (P < 0.001). Aspirin treatment led to an increase in mean arterial pressure (P < 0.001) and mean pulmonary arterial pressure (P < 0.005), but cardiac index, urine flow, platelets, leukocytes, fibrin degradation products, and cathepsin D levels remained similar to untreated controls. After infusion of PGI₂ there was a: (a) prompt increase of cardiac index to base-line levels; (b) late increase in mean arterial pressure (P < 0.005) after the discontinuation of PGI₂ treatment (c) restoration of urine output; (d) increase in circulating platelets to levels still below base line but above untreated control animals (P < 0.05); (e) no effect on circulating leukocyte levels; (f) fall in fibrin degradation products to 11.2 μg/ml (P < 0.05); (g) decline in cathepsin D levels to values 60% lower than the untreated controls (P < 0.025); and (h) reduction in plasma norepinephrine levels to base line at 4 h (P < 0.005). Although the mode of PGI₂ action is not clear, it is effective in the treatment of experimental endotoxemia.     

Selective hippocampal lesion following ω-conotoxin administration in rats

Histopathological evaluation of rat brains 3 days following unilateral i.c.v. injuections of ω-conotoxin GVIA (ω-ctx), 0.032 and 0.1 nmol/kg, was performed. An isolated unilateral lesion confined to the injected hemisphere was found in the hippocampal CA3 neurons. Morphometric analysis of these cells revealed a significant reduction in cell area in both dose groups compared to i.c.v. injected vehicle, and to the contralateral hemisphere. These data indicate a specific degenerative process and suggest that CA3 cells possess ω-ctx-sensitive Ca²⁺ channels which are essential to their viability.     

Controlled sleep restriction for rhythmic movement disorder

Rhythmic movement disorder is a parasomnia that is difficult to treat. In our study, 3 weeks of controlled sleep restriction with hypnotic administration in the first week resulted in almost complete resolution of the movements in 6 children. This therapeutic success suggests that rhythmic movement disorder results from a voluntary self-soothing behavior.     

In vitro antitumor reactivity of mononuclear leukocytes from cancer patients receiving immunotherapy with BCG

Mononuclear cell-mediated cytotoxicity (MCMC) against cultured tumor target cells was studied sequentially in melanoma and breast cancer patients before and during BCG administration. MCMC showed temporary fluctuations. In patients with locally advanced melanoma and carcinoma of the breast after tumor load reduction, the administration of BCG may increase the MCMC. This did not always correlate with a favorable clinical course. Potentiating serum factors appeared in 50% of these patients during BCG therapy, while blocking factors were rare. Neither correlated with prognosis. In patients with disseminated melanoma receiving chemoimmunotherapy, increases in MCMC may be related to clinical course. Blocking serum factors frequently developed in this group of patients and potentiating factors were rare. Neither correlated with the clinical course. Significant MCMC among normal donors and the apparent lack of specificity suggest a common non-specific (? natural) cellular reactivity against cultured tumor target cells.     

Active specific immunization in malignant melanoma

The effects of active specific immunization with nonirradiated autologous and irradiated cultured allogeneic melanoma tumor cells (TC) on cell-associated immunity was studied in 11 patients with widespread malignant melanoma receiving chemoimmunotherapy. Immunization with 1 × 10⁶-8 × 10⁷ TC was done in the draining area of a BCG scarification on day 7 of the study. The in vitro lymphocyte blastogenic response (BR) to autologous TC was studied in terms of the stimulation index on day 1, 7, 14, and 21. The stimulation index (SI) was the counts per min (cpm) in the TC stimulated culture minus the cpm among the TC alone divided by the cpm in the unstimulated controls. A positive BR was considered as a SI equal to or greater than 3. Six out of 11 patients had a significant increase in BR lasting 7-14 days after immunization. The pre- to post-immunization changes in the SI of the 6 patients were 2.5 to 7.5; 0.7 to 3.2; 0 to 5.2; 0 to 16; 0.1 to 6.6; and 6.5 to 30.0. Nine out of 11 patients showed a delayed local inflammatory reaction at the immunization site. Five out of 11 patients mounted a cutaneous delayed hyper sensitivity reaction to autologous tumor cells at a separate test site following immunization. There were no side effects. Active specific immunization in the drainage of a BCG reaction appears to be safe. Since a positive BR to autologous TC correlates with a good prognosis in patients with solid tumors, studies of the immunotherapeutic efficacy of this approach may be warranted.     

Influence of testosterone on gene expression in the ovariectomized mouse submandibular gland

Androgens exert significant effects on the murine submandibular gland. Our objective in this study was to determine the nature and extent of testosterone regulation of gene expression in the female submandibular gland, and to explore the degree to which this control is the same as in male glands. Ovariectomized female BALB/c mice were treated with placebo- or testosterone-containing hormone pellets for 14 d. Glands were collected and total RNA was isolated. Samples were analyzed for differential expression of mRNA using CodeLink microarrays, and the data were evaluated using genesifter. Testosterone significantly influenced the expression of over 500 genes, and while many (n = 214) of the genes were similarly differentially expressed in androgen-treated males, there were also many that were unique. These findings support our hypotheses that testosterone extensively influences gene expression in the female submandibular gland, and that the nature of this influence is variable between sexes.