Familial occurrence of gastric cancer in the 2-year experience of a population-based registry

The authors studied the familial occurrence of tumors in 154 individuals with gastric cancer by reviewing the clinical data and the genealogical tree of all patients registered in 1986 through 1987 in the Local Health Care District of Modena, Italy, for cancer of the stomach. Crude and age-adjusted (world population) incidence rates of gastric cancer were 34.0 and 21.4 new cases/100,000/year, respectively, in men, and 24.5 and 10.9 in women, respectively. Among first-degree relatives of the registered patients there were 30 cases of gastric carcinoma versus 15 cases in a control group matched for age and sex (Mantel-Haenszel odds ratio [M-H OR] 3.14, P less than 0.01). This excess of gastric neoplasms was observed in siblings (17 versus 7, M-H OR 4.33, P less than 0.02) but not in parents (13 versus 8, not significant). Besides gastric cancer, there was no significant excess of other type of tumors in case families. The familial occurrence of gastric cancer tended to be more frequent in patients with "diffuse" carcinoma (52%) than in subjects with "intestinal" cancer (33%), although the difference was not statistically significant. In conclusion, the current investigation suggests that a "family history" for gastric neoplasms is usually observed in approximately 10% to 15% of the registered cases. As already described for other common malignancies, therefore, the familial occurrence of gastric carcinoma suggests the existence of a genetic susceptibility to cancer of the stomach, at least in a fraction of these patients.     

Necrotizing fasciitis: case reports and review of the literature

Necrotizing fasciitis is a rare, rapidly progressing infection affecting the superficial fascia and the subcutaneous tissue, accompanied by severe systemic toxicity and multiorgan failure. It is caused by aerobic and anaerobic bacteria, occasionally in a synergistic polymicrobial combination (Type I Necrotizing Fasciitis); in other cases group A -haemolitic Streptoccoccus is the organism responsible for the infection (Type II Necrotizing Fasciitis). The infection often originates from small traumatic injuries or operative wounds and rapidly spreads especially in individuals with identifiable risk factors or immunocompromised patients. Sometimes necrotizing fasciitis occurs when no known portal of entry for bacteria is present. The increasing incidence of necrotizing fasciitis observed may reflect a resurgence of highly virulent mutant strains of group A beta-haemolitic Streptococcus. The pathogenesis, clinical features and treatment of the disease have been reviewed in the light of recent literature. We also report clinical data for four patients with necrotizing fasciitis. They show the importance of early diagnosis and rapid, aggressive and radical surgical intervention. High-dose broad-spectrum antibiotic therapy and intensive medical support are also required to avoid a fatal outcome.     

Focal neurological deficits in children with beta-thalassemia major

The hematologic disorder beta-thalassemia major is relatively common in Southern Italy. Stroke is a well described, though infrequently reported, complication of this disorder. We now report our experience regarding 300 children with beta-thalassemia major examined at the University of Catania, Italy, over a 20-year period. We encountered 9 patients (3%; 3 males, 6 females) with beta-thalassemia major who had hemorrhagic stroke. Two groups of patients can be identified: group 1 (2 patients 22%) with early-onset post-transfusion hemorrhage and group 2 (7 patients 77%) with delayed post-transfusion hemorrhage. In the first group, the hemorrhage occurred within 48 hours following blood transfusion. In the second group, hemorrhage occurred 7-15 days from last transfusion. In 5 patients out of 7 of this second group the first transfusion and ictal event both occurred after age five, suggesting prolonged chronic anemia might play a role in the hemorrhage.     

Effects of Hypericum extract on the acetylcholine release: a loose patch clamp approach.

The St. John's Wort (Hypericum perforatum) extract (Hp) represents one of the most useful natural therapeutic agents in the treatment of moderate and mild depression. The antidepressant effects of Hp are different, by a molecular mechanism point of view, when compared to those of other antidepressant drugs and, we think, a further pharmacological characterization is needed. It is suggested that the neurochemical effects of Hp could be bind either to its activity on the uptake of some mediators in the central nervous system or to the inhibition of some enzymatic activity at the receptor level. The present study carried out with the loose patch clamp (LPC) in the mouse neuromuscular junction, indicates a potentiation of the acetylcholine (ACh) action at the mouse neuromuscular junction. The spontaneous release of ACh was unaffected by Hp indicating that neither presynaptic nor postsynaptic function are modified by Hp. Indeed, both the frequency and the amplitude of the miniature end-plate currents (mepcs) were unmodified by Hp. Furthermore, the mepcs decay time (tau), i.e. the apparent cholinergic channel life time, was significantly increased after Hp treatment. The other parameter affected was the amplitude of the evoked end-plate currents (epcs) which was constantly and in a dose dependent manner increased by Hp. These findings suggest a possible action of Hp on the acetylcholinesterase (AChE) in terms of a reduction of the degradation rate of ACh.     

Reference Data of Vertebral Morphometry by X-ray Absorptiometry (MXA) in Argentine Women

Anterior, middle, and posterior heights and A/P and M/P ratios were determined from T5 to L4 in 111 normal Caucasian Argentine women from 20 to 70 years of age using dual energy X-ray absorptiometry (DXA) densitometry (Expert XL). Scanning time was less than 1 minute and the semiautomatic analysis requires ∼5 minutes. The precision error for the measurements ranged from 2.2% to 4.6%. The absolute precision error for heights was 0.6 mm. The vertebral bodies tended to be significantly larger in younger women than older women, especially for anterior and middle heights and the A/P and M/P ratios of the mid-thoracic vertebrae (T6–T10). There were no significant differences between pre- and postmenopausal women in the lumbar vertebral heights. It does not appear that this was a cohort effect because stature was identical in both age groups, and there was no age difference in posterior height. The Expert-XL software normalized the vertebral height based on the average height of the L2-L4 segment in order to minimize the influence of interindividual variation of body size. The average Z-scores for vertebral heights and ratios provided by the software were close to zero indicating that the normalization procedure appropriately corrected for smaller stature in Argentine women. Consequently, the reference values for morphometry X-ray absorptiometry (MXA) were appropriate for our population. In summary, we found that (1) in ``normal' women the anterior heights of the thoracic vertebrae (and therefore the A/P ratio) were higher in premenopausal than in postmenopausal women; and (2) the normalization approach corrected for differences of vertebral height and allowed utilization of the manufacturers software in our population. Received: 28 June 1999 / Accepted: 2 November 1999     

Differences in Bone Turnover and Skeletal Response to Thyroid Hormone Treatment Between Estrogen-Depleted and Repleted Rats

This study was undertaken to compare the effect of supraphysiological doses of thyroxine (T4) on bone metabolism in SHAM and OVX young adult rats. Female Sprague Dawley rats (220 ± 2 g, approx. 5 months of age) were divided into four groups of eight animals each. The animals were intraperitoneally injected 6 days per week with vehicle (Vh): 0.001 N NaOH/0.9% NaCl (SHAM+Vh and OVX+Vh) or 250 μg of thyroxine/kg/day (SHAM+T4 and OVX+T4) during a 5-week period. Serum T4 and osteocalcin (BGP), urinary pyridinolines (Pyr), and creatinine (creat) were determined. At the beginning and at end of the experiment, skeletal bone mineral content (BMC), bone mineral density (BMD), and area (A) of the total skeleton, femur, spine, and whole tibia, as well as proximal, middle, and distal areas of the tibia were assessed by dual X-ray absorptiometry (DXA) in an ultra-high-resolution mode. T4 treatment of the SHAM rats did not induce significant changes in BGP level or Pyr/creat excretion compared with the SHAM+Vh control group. However, these two biochemical bone markers significantly increased due to T4 treatment in OVX rats compared with both OVX+Vh and SHAM+T4 groups (P < 0.05 and P < 0.001, respectively). The OVX+T4 group had a significantly lower ΔBMD than SHAM+T4 rats in all studied regions (P < 0.05) except for the middle tibia region. OVX+T4 groups presented a significantly lower ΔBMC and ΔA compared with SHAM+T4 animals (P < 0.001). OVX+T4 rats significantly impaired the ΔBMD in the femur (P < 0.01), spine (P < 0.05), whole (P < 0.05) and middle (P < 0.05) tibia whereas T4 treatment of SHAM rats only affected, significantly, the whole (P < 0.05) and the proximal tibia region (P < 0.01). T4 treatment affects bone growth in young adult rats. The effect is significantly greater in the estrogen-depleted than in the estrogen-repleted state. The bone site most adversely affected by T4 treatment depends on the estrogen status. The proximal tibia (principally trabecular bone) was the most affected area in estrogen-repleted rats. Conversely, in OVX rats, the middle tibia (principally cortical bone) presented the greatest decrease in bone density. Received: 20 May 1999 / Accepted: 4 February 2000     

Depletion of inflammatory dendritic cells with anti-CD209 conjugated to saporin toxin

Monocytes rapidly infiltrate inflamed tissues and differentiate into CD209⁺ inflammatory dendritic cells (DCs) that promote robust immunity or, if unregulated, inflammatory disease. Previous studies in experimental animal models indicate that inflammatory DC depletion through systemic elimination of their monocyte precursors with clodronate-loaded liposomes ameliorates the development of psoriasis and other diseases. However, translation of systemic monocyte depletion strategies is difficult due to the importance of monocytes during homeostasis and infection clearance. Here, we describe a strategy that avoids the monocyte intermediates to deplete inflammatory DCs through antibody-loaded toxin. Mice with an abundance of inflammatory DCs as a consequence of lipopolysaccharide exposure were treated with anti-CD209 antibody conjugated to saporin, a potent ribosome inactivator. The results demonstrate depletion of CD209⁺ DCs. This strategy could prove useful for the targeted reduction of inflammatory DCs in disease.