William E. Josey

Genital herpetic infection association with cervical dysplasia and carcinoma

During a period of 5 1/2 years, 245 patients at Grady Memorial Hospital had cytologic evidence of an active genital herpetic infection. Cervical biopsies obtained in 98 of these patients showed a 23.7% incidence (58 cases) of cervical anaplasia, including 4 cases of invasive and 12 cases of in‐situ squamous cell carcinoma. This is in contrast with the 1.6% overall incidence of cervical anaplasia among a control group of 245 apparently noninfected women of similar age and background and the 2.7% incidence found in the total 56,418 women screened during this period. These findings suggest that either (1) similar factors operate independently to produce both conditions or (2) that the venereally transmitted (type 2) genital herpesvirus plays some etiologic role in precancerous and cancerous cervical lesions. Findings supporting one or the other theory are presented which, however, do not permit any firm conclusion. In either case, the results reported here indicate that women with known genital herpetic infection should be followed closely as a special group with an increased risk of developing cervical anaplastic changes.

Heparin therapy in septic pelvic thrombophlebitis: A study of 46 cases

Abstract Heparin anticoagulation was evaluated in 46 postpartum, postabortal, or postoperative patients with septic pelvic thrombophlebitis. Criteria for diagnosis, in addition to the characteristic temperature course, were radiologic evidence of septic pulmonary emboli (15 cases) or persistence of spiking fever despite antibiotic therapy. Response to heparin plus antibiotics was good in all but four patients, three of whom were found at laparotomy to have associated septic complications requiring surgical treatment. The fourth had a severe anaerobic streptococcus and bacteroides septicemia and died despite treatment which included inferior vena cava ligation and hysterectomy. Heparinization appears to be a safe and effectual alternative to venous ligation in the management of septic thrombophlebitis of the pelvic veins.

Role of Gardnerella vaginalis in the Pathogenesis of Bacterial Vaginosis: A Conceptual Model

BACKGROUNDnBacterial vaginosis (BV) is the most common cause of vaginal discharge and is associated with important public health complications such as preterm birth and acquisition or transmission of human immunodeficiency virus and sexually transmitted infections. Continued controversy concerning the pathogenesis of BV has led to a lack of progress in prevention and management of this infection.nnnMETHODSnDevelopment of a conceptual model for the pathogenesis of BV based on review of past and current research.nnnRESULTSnOur model suggests that BV is initiated by the sexual transmission of Gardnerella vaginalis, which has the appropriate virulence factors to adhere to host epithelium, create a biofilm community, and successfully compete with lactobacilli for dominance in the vaginal environment. The genetic diversity of G. vaginalis may result in virulent and avirulent strains. Symbiotic relationships with normally dormant vaginal anaerobes lead to increases in the latter which contribute to the symptoms of BV.nnnCONCLUSIONSnG. vaginalis is the pathogen responsible for the initiation of BV. Future research should focus on preventing its transmission and improved therapeutics for the biofilm infection that is caused by this pathogen and host anaerobes.

Viruses and cancer of the lower genital tract.

The importance of viruses as oncogenic agents in animals is well established. Recent work suggests that viruses may also be etiologically related to some human cancers. Herpes simplex virus type 2 (HSV‐2) and the genital wart virus are prime suspects in carcinomas involving the female lower genital tract. In particular, a close association has been found between HSV‐2 infection and cervical neoplasia in cytohistopathologic and seroepidemiologic studies. Preliminary results of prospective studies show further that women with genital herpetic infection are at increased risk of developing cervical neoplasia. Additional studies are also in progress on animal models, including subhuman primates, and efforts continue in the attempt to confirm the presence of viral genetic material or its expression in human cervical cancer cells. The possibility that human wart viruses have an oncogenic potential is suggested by clinicopathologic and electron microscopic observations. Further research is needed to ascertain the precise role of viruses in genital cancer.

Sarcomas after inoculation of newborn hamsters with Herpes virus hominis type 2 strains.

Summary Inoculation of newborn hamsters with virus doses greater than 103 TCD50 of types 1 or 2 Herpes virus hominis (HVH) strains caused a mortality approaching 100%. With lesser virus doses, nine sarcomas have been found 5–28 months after inoculation of four different noninactivated HVH type 2 strains and one other ultraviolet-inactivated type 2 strain. None of the animals inoculated with HVH type 1 strains developed tumors, and one newborn hamster inoculated intrathoracically with Eagles MEM developed a cheek-pouch well-differentiated fibrosarcoma. Eight of the nine tumors with HVH type 2 strains were at or close to the site of inoculation and the histological characteristics of some of these tumors differ from those associated with other viral-induced hamster sarcomas. No clear-cut evidence of a relationship between HVH and the tumors by a variety of virological and serological assays has been obtained as yet. The finding of C-type particles in two of three tumors or their explants by electron microscopy has raised further questions about the role of HVH in the causation of the tumors found.

Relation of Pock Size on Chorioallantoic Membrane to Antigenic Type of Herpesvirus Hominis

Summary Strains of herpesvirus hominis (HVH) which were recovered primarily from genital sites and which belonged to antigenic type 2 were found to produce large pocks (av diameter > 0.5 mm) on the chorioallantoic membrane (CAM) of embryonated eggs. Type 1 HVH strains isolated primarily from nongenital sites produced small pocks (av diameter < 0.5 mm) on the CAM. Histological examinations of the infected CAM have revealed that type 1 HVH strains produce ectodermal proliferation with little subectodermal involvement. Type 2 HVH strains involve ectodermal, mesodermal and endodermal layers with marked necrosis, hemorrhages and inflammatory cells. Multinucleated giant cells are more readily found in CAM infected with type 2 strains. The conflicting reports of other workers regarding pock size and histological findings after infection with various HVH strains may be explained by their multiple passages in eggs and other selective factors. Also included is a comparison of CAM infection with type 1 and 2 HVH and variola and vaccinia viruses. Evaluation of the pock size of freshly isolated strains of HVH which have had no prior egg passage could serve as a rapid presumptive test for ascertaining the antigenic type of HVH strains.

Corynebacterium vaginale (Haemophilus vaginalis) in women with leukorrhea.

Corynebacterium vaginale was recovered from vaginal-cervical swab specimens in 164 of 288 women with leukorrhea and in four of 30 women without signs or symptoms of lower genital tract infection. The amount and character of the leukorrhea observed in association with C. vaginale infection were variable; in typical cases the discharge had the appearance of a thin paste. In a series of 100 patients studied to determine the apparent causes of leukorrhea, noninfectious causes were inferred in seven patients and no cause ascertained in six. Candida or other yeasts, C. vaginale, and Trichomonas vaginalis were identified alone or in combination in 87 patients; 53 had yeasts, 35 had C. vaginale, and 15 had T. vaginalis.

Epidemiology of Herpes Simplex Viruses 1 and 2

Herpes simplex viruses (HSV) are among the most common infectious agents of man. There are at least two distinct serotypes (HSV-1 and HSV-2), which have different modes of transmission. HSV- 1 is transmitted chiefly via a nongenital route, whereas HSV-2 is most often transmitted venereally or from a mother’s genital infection to the newborn. The mode of spread of each of the two virus types is reflected by its relative prevalence at different ages and by its pattern of clinical distribution within the host. Thus HSV-1 infections occur most frequently during childhood and usually affect body sites above the waist. HSV-2 infections, on the other hand, occur most often during adolescence and young adulthood and involve body sites below the waist, primarily the genitals. Most infections in newborns are also caused by HSV-2.

Cephaloridine in septic abortion: Comparison with a conventional combined antibiotic regimen in a conservative program of management☆

Abstract Cephaloridine was compared with a conventional combined antibiotic regimen in the treatment of patients with septic abortion. The combination of penicillin and streptomycin was given to a group of 52 patients, 6 of whom also received chloramphenicol. Cephaloridine alone was administered to a second group of 44 patients. The approach to treatment in all cases was a conservative one, with deferment of curettage until infection had been controlled. Within the limitations of the study, cephaloridine was well tolerated and appeared to be equally effective in controlling sepsis due to a variety of organisms. Of special interest was the response to cephaloridine of 2 patients with Escherichia coli bacteremia, one of whom showed evidence of disseminated intravascular coagulation (Shwartzman-like reaction).

Reply to Hickey and Forney

TO THE EDITOR—We are pleased that our article prompted discussion on the path-ogenesis of bacterial vaginosis (BV) [1]. As a conceptual model with testable hypotheses , this was exactly what we had hoped for, to continue the dialogue on an important topic that has been stagnant until the recent emergence of new work on Gardnerella vaginalis from various investigators. As Hickey and Forney point out, there remain many questions about BV. Much of the discussion and debate, however, is based on semantics, for which a history of caring for thousands of patients with BV helps provide insight. First, let us reiterate that the title of our article states that it is a conceptual model that was put forth to stimulate discussion and further scientific investigation. Hick-ey and Forney point out that there are published data stating that G. vaginalis is found in healthy women [2]. Unfortunately , there is no definition of healthy vaginal flora. One logical definition might be that normal vaginal flora is acquired at birth, before the onset of any type of sexual activity that could transmit infectious agents to the vagina. The studies that are