Antioxidant supplementation effects on low-density lipoprotein oxidation for individuals with type 2 diabetes mellitus.

OBJECTIVE: This study compared susceptibility to oxidation of low-density lipoproteins (LDL) of non-diabetic and diabetic (Type 2) men and examined the response of diabetic men to antioxidant supplementation (alpha-tocopherol, beta-carotene and ascorbate). RESEARCH DESIGN AND METHODS: Twenty adult non-diabetic and 20 diabetic men were recruited. Oxidation of LDL was assessed by four different assay systems, and the extent of oxidation was assessed by four different measurements. Diabetic men received eight weeks of placebo ("baseline"), twelve weeks of antioxidant supplements ("treated") and eight weeks of placebo ("post-treatment"). Supplements provided 24 mg of beta-carotene, 1000 mg of ascorbate and 800 IU of alpha-tocopherol daily. RESULTS: With Cu oxidation at 37 degrees C, thiobarbituric reactive substances (TBARS) formation was significantly higher (p=0.032) and loss of free amine groups was significantly greater (p=0.013) in the LDL from diabetic subjects than controls. Antioxidant supplementation of diabetic subjects significantly decreased all parameters of LDL oxidation with Cu at 30 degrees C and 37 degrees C. At 30 degrees C the lag phase increased from 55 to 129 minutes (p<0.0001); conjugated diene formation decreased from 1.23 to 0.62 OD units (p<0.0001); TBARS formation decreased from 78 to 33 nmoles MDA/mg LDL protein (p<0.0001); and free amine loss decreased from 41 to 12% (p<0.0001). With Cu oxidation at 37 degrees C, similar changes occurred. CONCLUSIONS: These studies indicate that the LDL from diabetic subjects are more susceptible to oxidation than LDL from non-diabetic subjects. Supplementation of diabetic subjects with antioxidant vitamins significantly decreases susceptibility of LDL to oxidation by Cu. These studies are consistent with epidemiological and intervention studies suggesting that antioxidant vitamin use significantly decreases risk for coronary heart disease.     

Cancer-associated retinopathy

Patients with systemic cancer may have a variety of ocular complaints. Most commonly these are metastases or adverse effects of therapy. Paraneoplastic syndromes, like cancer-associated retinopathy, rarely cause ophthalmic symptoms. We describe a patient with a malignant mixed mullerian tumor and cancer-associated retinopathy who had circulating serum antibodies to recoverin and cells positive for recoverin in the tumor. We discuss the typical clinical symptoms as well as the pathophysiology of this uncommon disorder.     

Conformational preferences in a benzodiazepine series of potent nonpeptide fibrinogen receptor antagonists

Previously, we reported the direct design of highly potent nonpeptide 3-oxo-1,4-benzodiazepine fibrinogen receptor antagonists from a constrained, RGD-containing cyclic semipeptide. The critical features incorporated into the design of these nonpeptides were the exocyclic amide at the 8-position which overlaid the Arg carbonyl, the phenyl ring which maintained an extended Gly conformation, and the diazepine ring which mimicked the gamma-turn at Asp. In this paper, we investigate conformational preferences of the 8-substituted benzodiazepine analogues by examining structural modifications to both the exocyclic amide and the seven-membered diazepine ring and by studying the conformation of the benzodiazepine ring using molecular modeling, X-ray crystallography, and NMR. We found that the directionality of the amide at the 8-position had little effect on activity and the (E)-olefin analogue retained significant potency, indicating that the trans orientation of the amide, and not the carbonyl or NH groups, made the largest contribution to the observed activity. For the diazepine ring, with the exception of the closely analogous 3-oxo-2-benzazepine ring system described previously, all of the modifications led to a significant reduction in activity compared to the potent 3-oxo-1, 4-benzodiazepine parent ring system, implicating this particular type of ring system as a desirable structural feature for high potency. Energy minimizations of a number of the modified analogues revealed that none could adopt the same low-energy conformation as the one shared by the active (S)-isomer of the 3-oxo-1, 4-benzodiazepines and 3-oxo-2-benzazepines. The overall data suggest that the features contributing to the observed high potency in this series are the orientation of the 3-4 amide and the conformational constraint imposed by the seven-membered ring, both of which position the key acidic and basic groups in the proper spatial relationship.     

Regional distribution of retinal degeneration in patients with the proline to histidine mutation in codon 23 of the rhodopsin gene.

Mutations in the rhodopsin gene are associated with as many as one quarter of all cases of autosomal dominant retinitis pigmentosa (RP). A number of different rhodopsin mutations have been reported but only the proline to histidine mutation in codon 23 (Pro-23-His) has been well characterized clinically. One recent report described a "sectoral" distribution of the retinal degeneration associated with this mutation, while another reported only that pigment was present in all four quadrants in 13 of 17 patients. This asymmetric distribution of pigmentation and visual field loss may prove to be an important clinical sign of a type of RP with a relatively good visual prognosis. The authors present a family with Pro-23-His rhodopsin-associated RP in which all six affected individuals had a regional distribution of the retinal degeneration in which the inferior hemisphere of the retina was most severely affected.     

Millions to benefit from the Safe Medical Devices Act (SMDA) of 1990

The need and desire for quality improvements in patient care, coupled with consumer desire to assume increasing responsibility for their own healthcare, signals a strong future for services like the International Implant Registry.     

Barrier efficiency of surgical gowns. Are we really protected from our patients' pathogens?

Surgical gowns are traditionally worn to protect patients from contamination by the surgical team. Blood routinely covers gowns during surgery and often contaminates surgeons' undergarments and skin. Because of risks to the surgical team by blood-borne pathogens, disposable and reusable gowns were examined. To quantify "strike through," 1440 samples of gown fabric were tested against human blood in an apparatus designed to simulate abdominal pressure during surgery. Representative pressures (0.25 to 2.0 psi) and times (1 second to 5 minutes) were studied. Above 0.5 psi, spun-bond/melt-blown/spun-bond disposable products were more resistant than spun-lace cloth. New cloth gowns were better than those washed 40 times. Spun-bond/melt-blown/spun-bond fabric exposed to blood twice was more protective than spun-lace cloth challenged once. Gowns currently available exhibit varying resistance to strike through; only those with an impervious plastic reinforcement offer complete protection.     

The axial load teardrop fracture. A biomechanical, clinical and roentgenographic analysis

The anteroinferior cervical vertebral body corner fracture was originally described by Schneider and Cann as the "teardrop" fracture. This report analyzes the biomechanical, clinical, and roentgenographic features of 55 such fractures obtained from the National Football Head and Neck Injury Registry. Teardrop fractures resulting from tackle football characteristically occurred in players attempting to make a tackle in which initial contact was made with the top or crown of the helmet. There were two fracture patterns associated with the anteroinferior corner (teardrop) fracture fragment: 1) the isolated fracture, which is usually not associated with permanent neurologic sequelae; and 2) the three-part, two-plane fracture in which there is an associated sagittal vertebral body fracture as well as fracture of the posterior neural arch. This latter pattern was almost always associated with permanent neurologic sequelae, specifically quadriplegia. Axial loading of the cervical spine was clearly identified as a mechanism of injury for both fracture patterns. Roentgenographic examination must include both anteroposterior and lateral views with computed tomography or tomography as necessary to determine the presence of the sagittal vertebral body fracture and the integrity of the posterior neural arch.     

Compartment syndrome of the interosseous muscles: early recognition and treatment.

A compartment syndrome of the interosseous muscles can be a challenging diagnosis as there is generally no neurovascular compromise to the digits involved. The most sensitive clinical sign is pain with passive motion at the metacarpal phalangeal joint of the involved digit. In this report, a 31-year-old man developed a compartment syndrome of the first, second, and third dorsal interosseous muscles following an injection of heroin in the "snuffbox" area. Compartmental tissue pressure measurements were 80, 75, and 55 mmHg respectively, and were a significant aid in the early diagnosis as well as management.