Role of intraoperative angiography in the surgical treatment of cerebral aneurysms.

UNLABELLED: The benefit of using intraoperative angiography (IA) during aneurysm surgery is still uncertain. OBJECT: In this prospective study, the authors evaluate the radiographically demonstrated success of surgical treatment in 151 consecutive patients harboring 173 aneurysms who selectively underwent IA examination. The authors also assess the frequency with which IA led to repositioning of the aneurysm clip. METHODS: Intraoperative angiography was used selectively in this series, based on the surgeon's concern about the potential for residual aneurysm, distal branch occlusion, or parent vessel stenosis. Specific variables were analyzed to determine their impact on the incidence of clip repositioning and the accuracy of IA was evaluated by direct comparison with postoperative angiography (PA) in 90% of the cases in which IA was used. CONCLUSIONS: The selective use of IA led to successful treatment as shown by PA, with a low incidence of unexpected residual aneurysm (3.2%), distal branch occlusion (1.9%), and parent vessel stenosis (0%). Intraoperative angiography led to immediate repositioning of the aneurysm clip in 27% of the cases. Anterior cerebral artery aneurysms required clip repositioning less often and superior hypophyseal artery aneurysms required repositioning more often than aneurysms in other locations. Large and giant aneurysms required clip repositioning more often than small aneurysms; however, they were also more likely to display false success on IA as determined by PA. Aneurysms arising along the internal carotid artery were more likely to display successful clipping on IA, as determined by PA, than were aneurysms in other locations. The results of this series support the selective use of IA in the treatment of complex aneurysms, particularly large and giant aneurysms as well as superior hypophyseal artery aneurysms. As measured by PA, IA will improve the outcome of these patients.

Reducing the risk of rebleeding before early aneurysm surgery: a possible role for antifibrinolytic therapy.

Previous studies on the initial nonoperative management of aneurysmal subarachnoid hemorrhage (SAH) demonstrated that antifibrinolytic therapy reduced the risk of rebleeding by approximately 50%; however, prolonged antifibrinolytic treatment was associated with an increase in the incidence of hydrocephalus and delayed ischemic deficit. When early surgical intervention became routine for ruptured aneurysms, the use of antifibrinolytic therapy diminished. However, early surgery is generally performed in the first several days after SAH and the risk of rebleeding remains until the aneurysm is obliterated. Based on a review of the literature, the authors formed two hypotheses: 1) the high-dose intravenous administration of epsilon-aminocaproic acid (EACA), an antifibrinolytic agent, might reduce the risk of recurrent hemorrhage in the interval between SAH and early surgical intervention, and 2) a short course of EACA might not produce the increase in complications previously associated with its prolonged administration. The use of preoperative high-dose EACA therapy was evaluated in 307 patients to determine its safety and efficacy in reducing the incidence of rebleeding before early aneurysm surgery. All patients were admitted within 3 days of their SAH and were classified as Hunt and Hess Grades I to III. Only four patients (1.3%) suffered a recurrent hemorrhage. This compares favorably to the rebleeding rate of 5.7% reported for the early surgery group in the International Cooperative Study on the Timing of Aneurysm Surgery. The incidence of hydrocephalus or symptomatic vasospasm was not unduly elevated in patients receiving preoperative EACA. Thirty-five patients (11.4%) needed temporary cerebrospinal fluid drainage during their hospitalization and, overall, 8.8% required a ventriculoperitoneal shunt. The mean age of the patients who required a shunt was nearly 10 years older than the general study population. Seventy-one patients (23%) developed symptomatic vasospasm and 8.1% suffered a stroke. This study indicates that a brief course of high-dose EACA is safe and may be beneficial in diminishing the risk of rebleeding in good-grade patients prior to early surgical intervention. Further investigation is planned based on these promising results.

Anogenital warts in children.

Fourteen children presenting with anogenital (AG) warts and their close family members were studied; 28.6 and 8.3% of presenting children and other child household members, respectively, had non-genital cutaneous warts; 42.8% of children with AG warts had one or more adult household member with common hand warts. Fifty per cent of all mothers had subclinical cervical papilloma virus (PV) infection; only one male adult had subclinical PV infection of the penis without concurrent AG warts. Of the children with AG warts 42.8% had one or more adult household member with AG warts. Human papilloma virus (HPV) deoxyribonucleic acid (DNA), type 6/11 most frequently, was detected in 38.5% AG wart biopsies from children, and 67% AG wart biopsies from adults. HPV 31/33/35 was detected in 28.5% of cervical preneoplasias and type 6/11 in the one case of subclinical PV infection of the penile shaft. Detection of HPV types 6/11, 16/18, or 31/33/35 in AG warts in children was significantly associated with vertical (from an HPV-infected maternal birth canal during vaginal delivery) or sexual transmission of these warts (Fisher exact probability P = 0.031).

Human papillomavirus DNA detection in primary anogenital warts and cervical low-grade intraepithelial neoplasias in adults by in situ hybridization.

In this study, 58 consecutive patients with primary anogenital warts were selected from patients attending a genitourinary clinic. Patients were grouped on the basis of clinical lesion site, i.e. patients with genital warts only, patients with perianal or anal canal warts only, and patients with concurrent perianal and genital warts. Of these patients, 38% of the men (12/31) and 33.3% of the women (9/27) had other anogenital infections, such as nonspecific urethritis (NSU) or nonspecific genital infection, which were the most common. Of the patients who had perianal warts, 37% of the men (7/19) and 25% of the women (4/16) also had warts in the anal canal. Of the women who had anogenital warts, 63% (17/27) had concurrent subclinical low-grade cervical intraepithelial neoplasia (CIN) lesions. Human papilloma virus (HPV) DNA (either 6 or 11, 16 or 18, or 31 or 33 or 35) was detected in 53.3% (40/75) of the anogenital wart biopsy samples, and in 35.2% (6/17) of the low-grade CIN lesions. HPV types 6 or 11 were the most common types in anogenital warts (45.3%); and in CIN lesions HPV types 6 or 11 and 16 or 18 were found with equal frequency (17.6% each). There were no significant differences in HPV types between patients with genital warts and patients with perianal and anal canal warts. Anogenital infection with HPV is multicentric; external anogenital warts and subclinical CIN lesions often exist concurrently. The low prevalence of HPV DNA detected in anogenital warts and CIN biopsy samples may be due to insensitivity of the in situ hybridization technique used in this study.

A placebo controlled observer blind immunocytochemical and histologic study of epithelium adjacent to anogenital warts in patients treated with systemic interferon alpha in combination with cryotherapy or cryotherapy alone.

OBJECTIVE: To examine biopsy specimens of tissue immediately adjacent to anogenital (AG) warts which had been treated with either cryotherapy plus subcutaneous interferon (IFN) alpha 2a or cryotherapy alone, for histological features of (a) human papilloma virus (HPV) infection (b) localised cellular immune responses, to further characterise any cellular immune infiltrates with tissue immunocytochemistry, and to relate any histological, immunocytochemical findings to the treatment response of nearby AG warts. DESIGN: A randomised placebo controlled observer blind study. SETTING: Genitourinary Medicine clinic, Department of Immunopathology, Royal Victoria Hospital, Belfast, N. Ireland. SUBJECTS: Thirty patients with AG warts; 16 treated with IFN alpha 2a plus cryotherapy, and 14 treated with cryotherapy alone. OUTCOME MEASURES: (1) Light microscopic features associated with HPV infection and local cellular immune responses. (2) Indirect immunofluorescence detection of the following cell surface markers: HLA DR, alpha one antitrypsin, CD1, CD3, CD4, CD8, CD22. (3) Clinical response of AG warts to treatment. RESULTS: In pre-treatment biopsies only non specific indicators of HPV infection (acanthosis, 29/30 biopsies, and hyperkeratosis, 7/30 biopsies) were seen on light microscopy. Mononuclear cells were seen both throughout the upper dermis and centred around dermal blood vessels in 19/30 (63.3%) biopsies, and infiltrating into the epidermis in 12/30 (40%) biopsies. On indirect immunofluorescence CD3, CD8, CD4 antigen was detected on the surface of cells throughout the upper dermis in 24/29 (82.7%), 15/29 (51.7%), and 3/29 (10.3%), of biopsy specimens respectively. CD3 antigen, CD8 antigen and CD4 antigen was detected on the surface of cells infiltrating into the epidermis in 18/29 (62%), 7/29 (24.1%), and 6/29 (20.7%) of biopsy specimens respectively. CD1 antigen was seen on the surface of dendritic cells throughout the epidermis in all specimens; CD1 positive cells infiltrated into the upper dermis in 5/29 (17.2%). HLA DR was detected on the surface of dendritic cells throughout the epidermis in 22/29 (75.9%) of specimens, and on the surface of cells scattered both diffusely throughout the upper dermis and centred around dermal blood vessels in all specimens. Alpha one antitrypsin (A1AT) antigen was seen on the surface of cells in the upper dermis in 6/29 (20.7%) of biopsy specimens; no cells expressing CD22 surface antigen were seen. The nature of this local cellular immune response was not altered by treatment of nearby warts with either cryotherapy alone or cryotherapy plus systemic IFN alpha 2a, or related to the therapeutic outcome of these warts. CONCLUSIONS: (1) No convincing histological evidence of HPV infection was seen in epithelium surrounding AG warts. (2) A predominantly T cell-mediated immune response (the target of which is uncertain) was seen in this perilesional epithelium. (3) In the dosage regimens used in this study, treatment of AG warts with either systemic IFN alpha 2a plus cryotherapy or cryotherapy alone did not appear to augment localised cellular immune responses (against any presumed subclinical HPV infection) in epithelium surrounding AG warts.

Non-specific immunity in patients with primary anogenital warts treated with interferon alpha plus cryotherapy or cryotherapy alone.

Combination treatment of primary anogenital warts with subcutaneous interferon alpha 2a plus cryotherapy was no more efficacious than cryotherapy alone. Patients with primary AG warts showed no in vitro or in vivo suppression of non-specific immunity. In patients treated with interferon plus cryotherapy non-specific cellular immunity was stimulated, both in vitro and in vivo compared with patients treated with cryotherapy alone.

Ten year follow-up study of women presenting to a genitourinary medicine clinic with anogenital warts.

One hundred heterosexual women presenting at our clinic in 1979 with anogenital warts, were reviewed 10 years later. Median duration of warts following initial clinic attendance was 2 months (range 0-120 months). In 1979 cervical PAP smear results were available for 76 patients; cervical intraepithelial neoplasia (CIN) was seen in 15/76 (19.7%) women; 3 (4%) women had low grade CIN, 12 (15.7%) women had high grade CIN. Nineteen women had had treatment for CIN between 1979 and 1989, 7 laser ablation, 9 cone biopsy, 2 laser ablation and cone biopsy, and one woman laser ablation, cauterization and cone biopsy. At 10-year follow-up in 1989 4/100 women had anogenital warts, 12/100 women had cytological evidence of CIN (7 low grade, 5 high grade), and 37/100 women had CIN detected on colposcopic biopsy (31 low grade, 6 high grade). No women developed invasive cervical carcinoma during the study period. CIN lesions, detected in 1979, regressed without any treatment in 2 women. Colposcopic biopsy was 3.1 times more sensitive than single cervical PAP smear at detecting CIN (4.4 times as sensitive in detecting low grade CIN; 1.2 times as sensitive in detecting high grade CIN). In 1989 CIN was detected in 7/19 (36.8%) of women who had undergone cervical treatment between 1979 and 1989, and in 35/81 (43.2%) of women having no cervical treatment within this period (chi squared P greater than 0.5). These findings suggest that cervical laser ablative therapy and cone biopsy do not in the long term influence the natural history of cervical human papilloma virus-associated disease (CIN) in women with anogenital warts.(ABSTRACT TRUNCATED AT 250 WORDS)

Scissor excision plus electrocautery of anogenital warts in prepubertal children.

Nineteen prepubertal children with anogenital (AG) warts were treated by scissor excision plus electrocautery under general anesthesia. Median posttreatment follow up was nine months. Minor clinical recurrences were seen in five (26.3%) children, all within three months after treatment. Recurring warts responded in all cases to home application of 0.5% podophyllotoxin (Condyline). Surgery plus electrocautery was well tolerated with no notable side effects. It is simple, safe, and efficacious, and is a suitable second-line treatment for AG warts in children.

Subcutaneous interferon alpha 2a combined with cryotherapy vs cryotherapy alone in the treatment of primary anogenital warts: a randomised observer blind placebo controlled study.

OBJECTIVE: To compare patient tolerance and treatment efficacy of subcutaneous interferon (IFN) alpha 2a plus cryotherapy versus cryotherapy alone in treatment of primary anogenital (AG) warts. DESIGN: Randomised placebo controlled observer blind study. Statistical analysis was by chi square and Mann Whitney U tests. PATIENTS: 60 patients with newly diagnosed AG warts. INTERVENTION: 29 and 31 patients were treated with subcutaneous IFN alpha 2a plus cryotherapy or placebo injections plus cryotherapy, respectively. MAIN OUTCOME MEASURES: Clinical presence or absence of AG warts. Patients wart-free at 8 weeks were asked to re-attend at 12 weeks; those with persistent warts at 8 weeks were withdrawn from the study. RESULTS: At 8 weeks 60.7% (17/28 patients) of the IFN group and 67.9% (19/28 patients) of the placebo group were clinically wart-free (not significant); corresponding figures at 12 week review were 29.6% (8/27 patients) and 40% (10/25 patients) respectively (not significant). There was no difference in treatment response between males and females. Recurrence of warts at three month review, in patients cleared of warts at 8 weeks, was seen in 50% (8/16) and 37.5% (6/16) of patients in the IFN and placebo groups respectively (not significant). Multiple warts and the presence of perianal/anal canal warts, either alone or concurrent with warts on the genitalia, at first clinic attendance, were adverse prognostic indicators (p less than 0.001, and p = 0.05 respectively). Cervical human papilloma virus (HPV) infection, exophytic or subclinical, was present in 58.3% and 77.2% of females in the IFN and placebo groups respectively, at trial entry. Although these lesions were not directly treated, colposcopic resolution was seen in 12.5% of affected women, in both treatment groups, by the end of the 7 week treatment period. Systemic side effects were significantly more common in the IFN than in the placebo group, 50% versus 10.7% of patients (p less than 0.01). Severe influenza like symptoms occurred, after the first three injections only, in one patient treated with IFN; all other reported side effects were mild. CONCLUSIONS: Subcutaneous IFN alpha 2a combined with cryotherapy is no more effective than cryotherapy alone in the treatment of primary AG warts. The presence of multiple warts and perianal/anal canal warts are adverse prognostic indicators.

Comparative studies on the fermentative production of lantibiotics by staphylococci.

The production of the lanthionine-containing polypeptide antibiotics gallidermin from Staphylococcus gallinarum TU 3928 and pep 5 from S. epidermidis 5 is investigated with respect to regulation and stimulation of productivity by media components, optimization of both the media used and the fermentation process and is compared to the production of the lantibiotic epidermin from S. epidermidis TU 3298. Efficient methods for rapid quantification of lantibiotics, optimization of the media and a primary enrichment by adsorption chromatography are reported.

Pathophysiology and treatment of subarachnoid hemorrhage.

The pathophysiology and treatment of acute subarachnoid hemorrhage (SAH) are reviewed. SAH occurs when blood is released into the subarachnoid space, which surrounds the brain and spinal cord. Symptoms of SAH include severe headache, nausea, vomiting, neck pain, nuchal rigidity, and photophobia. The initial hemorrhage is fatal in 20-30% of patients. Complications of SAH include rebleeding, hydrocephalus, delayed cerebral ischemia associated with cerebral vasospasm, and seizures. The likelihood of rebleeding is increased by measures that rapidly lower intracranial pressure. The risk of developing hydrocephalus is associated with the volume of blood within the subarachnoid space and ventricular system. Cerebral vasospasm develops in 20-40% of patients, and up to 50% of affected patients die or suffer permanent neurological damage. Seizures occur in 5-15% of patients with SAH. Radiologic procedures form the foundation for the diagnosis of SAH. The most commonly used rating scale classifies the severity of SAH based on the clinical presentation of the patient. Surgery is the definitive treatment for the prevention of rebleeding. Hydrocephalus can only be treated surgically, most commonly by insertion of a drain. The only measures proved to be effective for treatment of delayed cerebral ischemia are volume expansion and the induction of hypertension. The calcium-channel blocker nimodipine was recently approved for treatment of arterial spasm in SAH. Intravenous nicardipine is also being studied for the same indication. These agents may improve clinical outcome substantially by limiting fixed neurological deficits. To prevent seizures, prophylactic antiepileptic therapy with phenytoin sodium is generally accepted. The SAH complications of rebleeding, hydrocephalus, delayed cerebral ischemia, and seizures are managed by surgical, drug, and fluid therapy.

Structural gene isolation and prepeptide sequence of gallidermin, a new lanthionine containing antibiotic.

Peptide antibiotics containing lanthionine and 3-methyllanthionine bridges, named lantibiotics are of increasing interest. A new lantibiotic, gallidermin, has been isolated from Staphyloccus gallinarum. Here we report the isolation of its structural gene which we name gdmA. In all lantibiotics so far studied genetically, three peptides can be formally distinguished: (i) the primary translation product, which we call the prepeptide; (ii) the propeptide lacking the leader sequence and (iii) the mature lantibiotic. Unlike the plasmid-coded epidermin, gdmA is located on the chromosome. The gdmA locus codes for a 52 amino acid residue prepeptide, consisting of an alpha-helical leader sequence of hydrophilic character, which is separated from the C-terminus (propeptide) by a characteristic proteolytic processing site (Pro-2 Arg-1 Ile1). Although pro-gallidermin differs from pro-epidermin (a recently isolated lantibiotic) only by a single amino acid residue exchange. Leu instead of Ile, the N-terminus of the prepeptide differs by an additional two exchanges.

Gallidermin: a new lanthionine-containing polypeptide antibiotic.

Gallidermin is a new member of the class of lanthionine-containing peptide antibiotics, which are summarized under the common name lantibiotics. The lantibiotic gallidermin is produced by Staphylococcus gallinarum (F16/P57) Tü3928, and it exhibits activities against the Propionibacteria, involved in acne disease. Gallidermin differs from the recently discovered tetracyclic 21-residue peptide antibiotic epidermin only in a Leu/Ile exchange in position 6. The isolation procedures for gallidermin included adsorption directly from the culture broth, ion-exchange chromatography of the amphiphilic and basic polypeptide followed by desalting, and final purification by reversed-phase HPLC. The structural elucidation of the polypeptide containing four thioether bridges involved mainly a combination of automated gas-phase sequencing, thermospray liquid chromatography/mass spectrometry and fast-atom-bombardment mass spectrometry.

Anogenital warts: epidemiology, treatment and association with cervical atypia.

In Northern Ireland in 1984 anogenital warts were diagnosed in 592 (352 male, 240 female) genitourinary medicine clinic attenders. Of these patients, 561 were heterosexual, 28 homosexual and three male bisexual. In the male patients 290 had penile warts, 67 meatal warts, 59 perianal warts, 25 anal canal warts and five rectal warts. In the female patients, 193 had vulval warts, 27 vaginal warts, 25 cervical warts, 107 perianal warts, 30 anal canal warts and one a rectal wart. Sexual partners were brought to the clinic by 345 patients and of these 93 male and 100 female partners had genital warts.The mean time from exposure to development of warts was 17 weeks SE +/- 1.5 (range 1 week - 12 months). As treatment, podophyllin 25% was used alone in 218 patients, and 132 were known to have had clearance of warts. At least one other sexually transmissible infection was found in 407 (69%) of patients. Cervical smears were taken in 164 women and were abnormal in 40 (24%). Cervical cytology was recorded in 89 regular sexual partners of male patients and was abnormal in 23 (26%).