Susceptibility of group A beta-hemolytic Streptococcus isolates to penicillin and erythromycin.

We have reevaluated the antibiotic susceptibilities of group A beta-hemolytic streptococci in view of recent reports of a high prevalence of erythromycin resistance in Japan and of an increase in penicillin treatment failures in the United States. A total of 474 isolates recovered during a 2- to 3-month period in 1980 were tested. All were susceptible by microtiter broth dilution to a penicillin concentration of less than or equal to 0.03 micrograms/ml (minimal inhibitory concentration), and 473 were killed by less than or equal to 0.06 micrograms/ml (minimal inhibitory concentration). Erythromycin minimal inhibitory concentrations showed a bimodal distribution: 95% were less than or equal to 0.06 micrograms/ml, and 5% were greater than or equal to 1 microgram/ml. Of the minimal bactericidal concentrations, 21% were greater than or equal to 1 microgram/ml and 3% were greater than or equal to 16 micrograms/ml. Group A beta-hemolytic streptococci remain susceptible to the inhibitory and bactericidal actions of penicillin, thus providing no in vitro explanation for the bacteriological relapses reported in some clinical studies. Unlike the Japanese experience, only 5% of our isolates were resistant to erythromycin (minimal inhibitory concentration, greater than or equal to 1 microgram/ml); however, 22% were tolerant (ratio of minimal inhibitory/bactericidal concentrations, greater than or equal to 32).     

Ultrastructural investigations of bone resorptive cells in two types of autosomal dominant osteopetrosis

In order to investigate the ultrastructure of bone resorptive cells in the two types of adult benign human osteopetrosis, iliac crest biopsies were obtained from 11 patients and 10 normal males, who served as a control group. Six patients had the radiological type I (4 women, 2 men, aged 23–58 years, MEAN = 36.5 years), and 5 type II disease (5 men, aged 20–48 years, MEAN = 29.8 years). The normal controls (aged 23–48 years, mean 34.1 years) were recruited from the medical staff. The biopsies were immediately divided. From each patient, half was embedded in paraffin for histochemistry and light microscopy, and half in epon for transmission electron microscopy.

The osteoclasts were markedly reduced in number and size hi Type I disease (0.2 ± .7 cells vs. 2.9 ± 1.0 cells per 2.7 mm² of bone area, p < 0.01) compared to controls, and stained only weakly for tartrate-resistant acid phosphatase (TRAP). At the ultrastructural level, no signs of active bone resorption were identified, whereas numerous mononuclear cells were observed at the bone surfaces.

In type II disease, the osteoclasts were large and highly multi-nucleated, with an increased number (8.3 ± 2.3 cells vs. 2.9 ± 1.0. cells per 2.7 mm² of bone area, p < 0.01) compared to controls. In all patients with this type, but never in type I or in the controls, a smooth, TRAP-positive substance was seen between the osteoclasts and the bone surface. Ultrastructurally, this substance was amorphous, with a condensation along the cell membrane. Neither ruffled borders nor clear zones were identified. Nuclear inclusions resembling tubular structures were observed in some osteoclasts in all patients with type II disease.

It is concluded that characteristic differences exist between the two types of adult human osteopetrosis at the ultrastructural level. Type I is morphologically similar to some murine mutations characterized by defective maturation of bone resorptive cells. In type II, a defect in the resorptive capacity of their giant osteoclasts is proposed. The pathogenetical significance of nuclear inclusions in type II osteoclasts is unknown.     

Chemokine expression and leucocyte infiltration in Sjogren's syndrome

OBJECTIVE: To investigate the expression and source of chemokines in minor salivary gland biopsies (MSGs) in patients with Sjogren's syndrome (SS). METHODS: Immunohistochemical analysis was used to determine the pattern of chemokine expression in MSGs from patients with (n=6) and without (n=5) SS, as well as to examine the phenotype of both resident and infiltrating cells expressing chemokines. RESULTS: Significant differences in the number of infiltrating mononuclear (MN) cells in patients with and without SS were noted. Ductal epithelial cells of SS biopsies expressed significantly increased levels of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, interleukin-8 (IL-8) and RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted). Biopsies from patients with SS showed that MIP-1beta was expressed by 51% of infiltrating cells, while 41% expressed MIP-1alpha, whereas 22 and 7% expressed RANTES and IL-8, respectively. CONCLUSION: Chemokines expressed by ductal epithelial cells may attract circulating leucocytes, in particular CD4+ T cells, towards the site of inflammation, thereby orchestrating the influx of MN cells characteristically seen in MSGs in SS. Chemokines may be induced directly by a putative triggering agent for SS, or secondary to the release of pro-inflammatory cytokines produced by epithelial cells. These findings further implicate epithelial cells as playing a major role in the pathogenesis of SS and implicate chemokines in the leucocyte recruitment in this setting.      

Effect of dietary cholesterol on biliary lipids in patients with gallstones and normal subjects

The purpose of this study was to determine the effect of dietary cholesterol on biliary lipids in subjects with and without gallstones. Twelve patients with asymptomatic gallstones (six men, six women) were assigned diets containing 500, 750, and 1000 mg cholesterol daily for 3-wk periods in random sequence. Seven healthy women similarly were assigned diets containing 500 and 1000 mg cholesterol daily. With increasing dietary cholesterol in patients with gallstones, biliary saturation indices and molar percents of cholesterol and phospholipids increased significantly while molar percent of biliary bile acids decreased significantly. With increasing dietary cholesterol in healthy women, the biliary saturation index and molar percent of cholesterol increased significantly; the mean saturation index exceeded unity on the diet containing 1000 mg cholesterol daily. In conclusion, augmented dietary cholesterol for brief periods increased biliary cholesterol saturation in subjects with and without gallstones.     

Tolerance to and cross tolerance between ethanol and nicotine

Female DBA mice were subjected to one of four treatments: ethanol-containing or control diets, nicotine (0.2, 1.0, 5.0 mg/kg/hr) infusion or saline infusion. After removal from the liquid diets or cessation of infusion, the animals were challenged with an acute dose of ethanol or nicotine. Chronic ethanol-fed mice were tolerant to the effects of ethanol on body temperature and open field activity and were cross tolerant to the effects of nicotine on body temperature and heart rate. Nicotine infused animals were tolerant to the effects of nicotine on body temperature and rotarod performance and were cross tolerant to the effects of ethanol on body temperature. Ethanol-induced sleep time was decreased in chronic ethanol- but not chronic nicotine-treated mice. Chronic drug treatment did not alter the elimination rate of either drug. Chronic ethanol treatment did not alter the number or affinity of brain nicotinic receptors whereas chronic nicotine treatment elicited an increase in the number of [3H]-nicotine binding sites. Tolerance and cross tolerance between ethanol and nicotine is discussed in terms of potential effects on desensitization of brain nicotinic receptors.     

The pathophysiology of gastric surgery.

Gastric surgery may be followed by mechanical postoperative problems, usually due to impaired gastric emptying or the afferent loop syndrome, recurrent dyspepsia, the early or late dumping syndrome, diarrhoea, or nutritional disturbances. The pathophysiological basis of these disorders is discussed and their clinical features are briefly considered.