Sublingual vaccination and delivery systems.

Most infectious agents use mucosal tissues as entry portals, thus, mucosae are frequently defined as a first line of defense against pathogens. Mucosal protection generally operates through antibody-mediated and cytotoxic T-cell responses which can be triggered by mucosal vaccines. Sublingual vaccination provides many advantages such as systemic and mucosal responses (both locally and at remote mucosal sites), besides being a needle-free administration route with high patient compliance and limited adverse effects. Buccal mucosa complexity nonetheless represents a challenge for vaccine administration, hence, many efforts were recently deployed to improve vaccine components, mucoadhesion and/or penetration. Several innovative approaches indeed confirmed that a robust and protective immunity can be achieved by sublingual vaccines. This review will then specify the most recent delivery systems and improvements developed to increase sublingual vaccines efficiency. We will focus our description on the immune mechanisms involved and the requirements for optimal sublingual immunization and mucosal protection.

Sudden death associated with very low calorie weight reduction regimens.

We studied the cases of 17 individuals who died suddenly of ventricular arrhythmia after prolonged use (median 5 months) of very low calorie weight reduction regimens consisting entirely or largely of protein. The deaths appeared to be independent of type of medical supervision received during the diet, daily dosage of potassium supplementation, and biological quality of the protein product used. Factors common to all cases were marked obesity at the onset of dieting, prolonged use of extremely low calorie diets (approximately 300 to 400 kcal daily), and significant and rapid weight loss. Our review of available electrocardiograms and pathological specimens revealed a pattern of cardiac changes previously described in starvation. We conclude that use of very low calorie weight reduction regimens should be curtailed until further studies determine what modifications, if any, can insure their safety.

A rabbit model of toxic shock syndrome: clinicopathological features.

The complete pathogenesis of toxic shock syndrome (TSS) has yet to be elucidated. Unmasking the complex interactions among bacterial products, host factors, and possibly tampon components requires a suitable in vivo model. For this purpose, subcutaneous chambers implanted in rabbits were inoculated with Staphylococcus aureus isolated from patients with TSS. Infected rabbits developed illness characterised by multisystem involvement that included periportal inflammation of the liver, erythrophagocytosis in the spleen and lymph nodes as well as extreme vascular dilatation and epithelial lesions similar to those described in patients with TSS. Concentrations of serum creatinine (P less than 0.03) and triglycerides (P less than 0.04) were significantly raised in rabbits infected with TSS strains compared with rabbits infected with non-TSS strains of S. aureus. Both TSS and non-TSS strains of S. aureus produced fever and diarrhoea, but TSS strains were significantly (P less than 0.05) more lethal and more likely to produce respiratory distress and lowered blood pressure. This model may help to prove or disprove proposed mechanisms for the development of TSS.

Histologic changes seen in the hepatic parenchyma and in metastatic nodules following hepatic dearterialization.

Hepatic dearterialization was performed on four patients in an attempt to provide symptomatic relief from metastic carcinoma in the liver. Interruption of hepatic arterial blood supply causes necrosis in larger metastatic tumor deposits, but very small nodules are unaffected by the procedure; this observation supports experimental studies on tumor angiogenesis factor. Interruption of hepatic arterial blood supply results in nonspecific ischemic changes to the hepatic parenchyma, which responds with small nests of regenerating liver cells. This finding appears to support the work of Plengvanit on revascularization of the liver after hepatic artery ligation.

Seasonal variation in spontaneous abortions.

Using a national sample of hospital discharges, we found identical seasonal patterns for spontaneous abortions and conceptions but no significant seasonal variation in the rate of spontaneous abortions per 1,000 conceptions. The differences between our findings and those of previous investigators of spontaneous abortion may reflect our more comprehensive definition of spontaneous abortion, our more complete estimate of the monthly number of conceptions, and our more rigorous statistical analysis. The periodic regression analysis (PRA) reported in our study may be useful in other studies that monitor short-term trends.

Dearterialization of the liver for metastatic cancer. Clinical, angiographic and pathologic observations.

Five cases of dearterialization of the liver for metastatic cancer are presented. Subjective and objective improvement was accomplished in three patients. Pre- and postoperative arteriography demonstrates the extent of devascularization and the routes of reestablished collateral. Microscopic studies demonstrated effects on tumor and on hepatic parenchyma and biochemical data indicate the extent and duration of hepatic dysfunction.

Pathologic findings in twelve fatal cases of toxic shock syndrome.

Pathologic changes in 12 fatal cases of toxic shock syndrome occurred in the vagina, cervix, lung, liver, and kidney. Desquamation and ulceration of the cervical and vaginal mucosa were seen in all six cases where adequate specimens were submitted. Hyaline membrane formation characteristic of "shock lung" was found in all lung tissues. Periportal inflammation was found in all liver specimens and acute tubular necrosis was seen in eight of the 12 kidney specimens. Although not specific for toxic shock syndrome, the findings are consistent with the hypothesis that the illness is caused by a staphylococcal toxin.

Fatal nosocomial Legionnaires' disease: clinical and epidemiologic characteristics.

The occurrence, clinical, and epidemiologic characteristics of fatal nosocomial Legionnaires' disease were ascertained by examining a sample of autopsy specimens submitted by hospitals participating in the National Nosocomial Infections Study. Sections of lung tissue from 263 patients were submitted by 40 hospitals in 24 states. Legionnaires' disease was identified in 10 patients (3.8%) from six hospitals in five states. The clinical and epidemiologic characteristics of sporadic fatal nosocomial Legionnaires' disease were similar to those from cases that occurred during epidemics of Legionnaires' diseases. A case-control study showed that cases of Legionnaires' disease were associated with an increased occurrence of Legionnaires' disease during the period June through November, temperatures greater than 39.2 degrees C, and administration of corticosteroids before onset of pneumonia. Legionnaires' disease can occur as a fatal nosocomial pneumonia and has clinical and epidemiologic features that may be helpful in differentiating it from nosocomial pneumonia of other causes.

Fatal-cat trasmitted tularemia: demonstration of the organism in tissue.

The case reported represents an unusual mode of transmission of tularemia from cat to man, with fatal outcome. The use of the modified Dieterle spirochete stain demonstrated F tularensis in tissue when all other routine stains failed. Direct immunofluorescent staining confirmed the presence of the organism in tissue sections. F tularensis and the etiologic agent of Legionnaires' disease are similar only in their ability to stain with the modified Dieterle stain and their inability to stain with conventional histochemical technics.

The diagnosis of ovarian cancer by pathologists: how often do diagnoses by contributing pathologists agree with a panel of gynecologic pathologists?

The Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study of ovarian, breast, and endometrial cancer in women 20 to 54 years of age, permitted the diagnoses of contributing pathologists to be compared with those of a panel of three gynecologic pathologists. A diagnosis of ovarian cancer was made by contributing pathologists on 477 subjects. Agreement between the two groups of pathologists was 97% for primary epithelial ovarian cancer and 89% for primary nonepithelial ovarian malignancies. Agreement on diagnosis of major cellular subtypes of ovarian malignancy ranged between 73% for endometrioid cancer and 100% for clear cell carcinomas. We conclude that the diagnosis of pathologic features of primary ovarian cancer is highly predictable. Nonetheless, diagnosis by histologic type varies sufficiently that a review process should be considered for clinical or investigative decisions involving specific histologic diagnoses of ovarian cancer.