Comparative effects of different doses of ribavirin plus interferon-alpha2b for therapy of chronic hepatitis C: results of a controlled, randomized trial.

Compared to either drug alone, therapy with the combination of ribavirin and interferon-alpha leads to improved rates of response in patients with chronic hepatitis C. Side effects often mandate downward dose adjustment or cessation of therapy, and the optimal dose of ribavirin has not been established. The aim of this study was to learn whether 600 mg ribavirin per day would prove as efficacious as 1,000-1,200 mg/day when combined with interferon (3 million units thrice weekly) for therapy of patients previously treated with standard interferon who had failed to respond or who had relapsed. We enrolled 69 patients with chronic hepatitis C and compensated liver disease: 45 were men, 65 were Caucasian, 48 were infected with genotype 1 hepatitis C virus. By random assignment, 35 received 600 mg ribavirin/day (group A), whereas the other 34 received 1,000 mg (< or = 75 kg body wt) or 1,200 mg/day (>75 kg body wt) (group B). At baseline, the two groups were well matched for demographic and laboratory features. In both groups, mean serum levels of alanine aminotransferase (ALT) and hepatitis C viral (HCV) RNA levels fell promptly and remained significantly lower than baseline throughout 24 weeks of therapy. There was no significant difference in mean levels of ALT or HCV RNA during therapy or at the end of follow-up (24 weeks after cessation of therapy). At the end of 24 weeks of posttherapy follow-up, 12 patients in each group had undetectable HCV RNA in serum, whereas 11 (31%) in group A and 9 (26.5%) in group B had normal serum ALT levels. The lower doses of ribavirin (group A) were tolerated better. In conclusion, in previous nonresponders or relapsers to interferon done, combination therapy with interferon-alpha2b (3 MU thrice weekly) + 600 mg ribavirin/day is tolerated better and is as effective as interferon plus higher (standard) doses of ribavirin (1,000-1,200 mg/day).

The subcranial approach for the treatment of cerebrospinal fluid rhinorrhea: a report of 10 cases.

PURPOSE: Because of the likelihood of meningitis and other intracranial complications, optimal treatment for a cerebrospinal fluid (CSF) fistula is to close the leak. The neurosurgical approach to the management of CSF rhinorrhea has been by intracranial access. Extracranial approaches are now gaining acceptance as the preferred method for initial treatment of CSF leakage, because the success rates are reasonable, and the morbidity is lower. This report describes the results of using such an approach. PATIENTS AND METHODS: The extended subcranial approach was used in 10 patients with CSF rhinorrhea. Selection criteria included defects of the anterior skull base greater than 15 mm in diameter, defects not accessible by endoscopes, fistula sites that could not be localized preoperatively, and multiple and transverse fractures of the cribriform region. Follow-up ranged from 8 to 23 months, with a mean of 17 months. RESULTS: Resolution of rhinorrhea was achieved in 9 (90%) of the patients. Anosmia was the only postoperative complication, occurring in 8 patients. CONCLUSION: The authors conclude that the extended subcranial approach to the anterior skull base is a safe, versatile, and effective procedure for the surgical treatment of CSF rhinorrhea involving the anterior skull base.

Supraorbital burr hole via a glabellar incision: a simple approach to anterior skull base.

A left subfrontopolar lesion with marked edema was totally resected utilizing a minimally invasive approach. It was possible to expose and resect the lesion, which turned out to be a tuberculoma, through a burr hole placed supraorbitally through a glabellar incision. The development and significance of minimalization techniques for surgery in the skull base region are discussed.

[The subcranial approach to the anterior skull base. Retrospective study of 75 cases]. / La voie d'abord sous-crâniale de l'étage antérieur de la base du crâne. Etude rétrospective de 75 patients.

We reviewed the cases of 75 patients who underwent an extended subcranial approach to the anterior skull base for treatment of various tumors (35 patients), repair of craniofacial trauma injury (33 patients), or cerebrospinal fluid leakage (10 patients). Preoperative evaluation and surgical procedures were reassessed. Significant complications in the oncology group consisted of one hematoma requiring aspiration, 2 cases of transient pneumocephalus, 2 osteocutaneous fistulae and 2 epiphoras. In the trauma group, one patient died from intracerebral damage, 2 presented with transient pneumocephalus, 5 with telecanthus and 5 with enophthalmy. The most frequent late complication in all three groups was anosmia. Based on this review, we feel that this technique is a safe and effective procedure for the surgical treatment of various pathological conditions involving the anterior skull base.

Harvesting large fascia lata sheaths: a rational approach.

This article describes an "S"-shaped incision for the open approach of harvesting wide sheets of fascia lata with reference to the important anatomical landmarks. Forty-three patients required dural replacement in cases of tumors, trauma, or cerebrospinal fluid leak involving the anterior skull base. The extended anterior suberanial approach to the skull base was used for all patients. Early functional status of the operated limb in seven of the patients treated first was assessed by physical examination and then by means of the computerized Kinetic Communicator (Kin-Com; Medex Diagnostics, Canada) dynamometer. None of these patients suffered any significant immediate complications and had good results at the preliminary functional assessment. All other patients were evaluated clinically for functional deficits of the operated lower limb to further assess its morbidity. The technique described herein was shown to enhance the case and control of fascia lata harvesting. It affords low complication rate and donor limb morbidity. Donor limb morbidity did not have any deleterious effect on the patients' normal daily activities and only became apparent during strenuous physical activity.

Early outcome and complications of the extended subcranial approach to the anterior skull base.

OBJECTIVES: To present the technique of the extended subcranial approach to the anterior skull base and to review the results in 55 patients who underwent the procedure. STUDY DESIGN: Retrospective review of the records of 55 patients who underwent the extended subcranial approach to the anterior skull base between 1994 and 1998 for the treatment of various neoplasms originating in the nasal cavity, nasopharynx, paranasal sinuses, orbit, or meninges, as well as for the repair of complex craniofacial trauma and/or cerebrospinal fluid (CSF) leak. Preoperative patient evaluation and the surgical technique are also reviewed. METHODS: Patient records were retrospectively reviewed and tabulated for age, sex, and indications for procedure, with special focus on early outcome and complications. RESULTS: Twenty-six patients underwent oncologic resections, 22 patients had reduction of complex fronto-naso-orbital and skull base fractures, and seven patients had repair of CSF leak. Significant complications in the oncologic group consisted of one hematoma requiring needle aspiration and two cases of temporary nontension pneumocephalus. In the fracture group, one patient died because of extensive intracerebral damage and multiorgan failure, and one patient had nontension pneumocephalus coupled with CSF leakage and one patient had temporary nontension pneumocephalus. The most common late complication in all three groups was anosmia. CONCLUSIONS: Based on their review, the authors conclude that the extended subcranial approach to the anterior skull base is a safe, versatile, and effective procedure for the surgical treatment of various pathological conditions involving the anterior skull base.

Intrapancreatic ciliated enteric duplication cyst presenting with biliary obstruction.

A 46-yr-old man presenting with biliary obstruction from an intrapancreatic tumor underwent pancreaticoduodenectomy. The pathology report showed the tumor to be an enteric duplication cyst. Diagnostic imaging features and operative management are discussed.

Cytomegalovirus gastritis associated with pseudolymphoma.

A man who previously had several episodes of upper gastrointestinal hemorrhage from erosive gastritis developed recurrent hemorrhage. Endoscopy showed punctate hemorrhages in the fundus and body of the stomach, plus a discrete area of thickened folds in the anterior wall. Biopsies revealed a dense mucosal infiltrate that included cytomegaloviral inclusions. Bleeding continued despite treatment with blood transfusions and ranitidine. Because of continued hemorrhage, and to distinguish the cause of the thickened folds, surgical biopsy was performed that showed lymphoid germinal formations, characteristic of pseudolymphoma. He responded to i.v. ganciclovir and has had no further bleeding during 2 years of follow-up.

Hemispheric supratentorial low-grade astrocytoma.

The records of 57 patients who were operated on at the Beilinson Medical Center from 1970 through 1982 for supratentorial low-grade astrocytomas were reviewed. The management of these patients was correlated with survival. Our study demonstrates that a younger age at onset and a negative radionuclide uptake on isotope scan, were the most important factors associated with a better survival rate. Extensive tumor resection combined with radiation therapy also exercised a beneficial effect in prolonging survival.

[Outcome of immediate management of severe head injuries].

Immediate management of severe head injuries still poses a serious challenge. 50 patients with severe head injuries (Glasgow Coma Scale, 8 or less) were treated from February 1, 1989 to April 30, 1990. The effects of age, Glasgow Coma Score at admission, CT findings, pupillary reactivity to light and intracranial pressure on outcome, were evaluated. The results of the present series match those of other studies and in some aspects the results are even superior. We attribute the high incidence of good outcome to the direct referral of the severe head injury patients, thus excluding delays at peripheral hospitals. In addition, aggressive management in the intensive care units and a broader range of indications for operation were also correlated with favorable outcome.

Haemangiopericytoma presenting with intracerebral haemorrhage. Case report and review of literature.

A case of an intracerebral bleeding from haemangiopericytoma is reported. To our knowledge it is the first published case. The literature concerning apoplectic presentation of brain tumours is reviewed.

The ambivalent effects of early and late administration of mannitol in cold-induced brain oedema.

This study was undertaken in order to determine whether early administration of mannitol is different from late administration in its effect on brain oedema. Cold-induced brain oedema, which was confirmed by high resolution CT scan, was produced in 2 groups of cats. In group one mannitol was given early (90 minutes after injury); in group two 3-4 hours after the injury (late). Repeated CT scans following mannitol administration showed that the early group exhibited significantly greater dehydration (p less than 0.0001) while the late group showed significant hydration, in the lesioned hemisphere. The contralateral control hemisphere responded to mannitol with similar dehydration effect in both groups.

Effects of phototherapy on the activity of microsomal mixed-function monooxygenases and the pharmacokinetics of [14C] hexobarbital in jaundiced and heterozygous Gunn rats.

We assessed the effects of in vivo phototherapy of Gunn rats on the activity of hepatic microsomal mixed-function monoxygenases and on the in vivo pharmacokinetics of [14C]HB. In experiment 1 no serial changes were seen in activities of hexobarbital hydroxylase or benzo(a)pyrene hydroxylase in hepatic microsomes isolated after 2, 4 or 7 days from homozygous jaundiced female Gunn rats exposed to continuous phototherapy or in matched Gunn rats maintained under dim light. In experiment 2 homozygous jaundiced (jj) and heterozygous nonjaundiced (Jj) Gunn rats of both sexes each received i.v. [14C]HB on 2 successive days. In random order, each was exposed on the first or second day to phototherapy for 5.5 hr, beginning 0.5 hr before the administration of HB; otherwise, each was kept under dim light. Plasma [14C]HB in arterial blood samples was separated chromatographically from its labeled metabolites, and biexponential plasma disappearance curves for [14C]HB were analyzed by a SAAM-23 computer program. Clearances in female rats were much slower. In both sexes, the total body clearance and volume of distribution of HB were decreased by 20% during phototherapy of the jj but not the Jj rats; terminal plasma half-life was unchanged. In experiment 3 direct in vitro illumination of [14C]HB did not cause photodegradation of this compound, despite the presence of albumin with or without bilirubin.

Familial glioblastoma multiforme without neurofibromatosis.

Glioblastoma multiforme is a rapidly growing anaplastic primary tumor of the central nervous system. It is frequently associated with neurofibromatosis or other hamartomatous syndromes, and in such kindreds may be found in several generations. We describe a highly inbred family in which glioblastoma multiforme presents in males only as an isolated central nervous system neoplasm on the right side, without evidence of other underlying genetic disease. It is speculated that in this family the tumor develops as the consequence of an autosomal recessive or an X-linked recessive mutation. In addition, the gene for cystic fibrosis segregates in this family and an undefined autosomal recessive malformation syndrome was detected.

The advantages of the 30-cm flexible sigmoidoscope over the 60-cm flexible sigmoidoscope.

To determine the optimal length of the flexible fiberoptic sigmoidoscope we performed a randomized, blinded comparison study of the standard 60-cm instrument with a prototype 30-cm instrument with identical design features. Ninety-six male patients referred for symptom evaluation underwent examination with both instruments in random order by different examiners; positive examinations were followed by colonoscopy or surgery. Performance of the 30-cm sigmoidoscope compared with the 60-cm instrument revealed that the former was significantly more likely to yield a complete examination (74 vs. 32 examinations, p less than 0.002), took less time to perform (6.4 vs. 9.8 min, p less than 0.0001), and was more acceptable to patients and physicians. The 30-cm instrument was not significantly less effective than the 60-cm instrument in detecting polyps (21 vs. 25), adenocarcinoma (six for each), and inflammatory lesions. For these reasons, we conclude that the 30-cm flexible sigmoidoscope has a role in the evaluation of colorectal complaints.

Neurosurgical management of single brain metastasis.

A series of 74 consecutive cases undergoing craniotomy for single brain metastasis in the Beilinson Medical Center between October 1975 and October 1981 were reviewed. All patients underwent radiation therapy after craniotomy. The most common metastasis was that of unknown origin (35%), followed by lung (24%) and breast (16%). Overall median survival after craniotomy was 6.6 months. Overall 1- and 2-year survival rates were 30 and 15%, respectively. Operative mortality (30 days) was 15%. For the patients with metastases to the lung, median survival was 7.5 months and 1-year survival rate was 33%. It appears from this report that two dominant factors affect the prognosis of these patients. The first is the long latent interval (time between diagnosis of primary tumor and detection of metastasis). The second is the location of the metastasis; those with lesions in the cerebral hemispheres had a far better outcome than those with cerebellar lesions (p less than 0.0001).

Multicentric gliomas of brain and spinal cord.

The clinical and histopathological findings in a child suffering from both cerebral and spinal gliomas of differing histological types are described. There was a family history of von Recklinghausen's neurofibromatosis. The possibility of overlooking the symptoms and signs pointing to a spinal cord lesion in the presence of a known intracranial tumour is stressed.