Sequential gradient pneumatic compression enhances venous ulcer healing: a randomized trial

The treatment of venous ulcers has remained largely unchanged for centuries. The application of properly applied graduated compression bandages, the use of graduated compression stockings, and surgery have been shown to achieve healing. However, some ulcers persist despite appropriate management. A randomized study was undertaken to compare two regimens of treatment for such patients. Both regimens included ulcer debridement, cleaning, nonadherent dressing, and graduated compression stockings. In one regimen, sequential gradient intermittent pneumatic compression was applied for 4 hours each day. Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group. The median rate of ulcer healing in the control group was 2.1% area per week compared to 19.8% area per week in the intermittent pneumatic compression group. The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers.     

Chronic venous insufficiency disease

Chronic venous insufficiency is a debilitating condition. It affects about 0.2% of the population and is very demanding on health resources. In the UK, there are about 100,000 patients with active leg ulcers and treating these patients costs the national health service between £100 and £400,000,000 per anum. This paper reviews the classification, epidemiology, pathophysiology, investigations and treatment of this condition. The etiology of venous ulceration is discussed and the various theories explaining the cause of ulceration examined. The latest research into the condition is reviewed and the relative roles of superficial venous incompetence and deep venous incompetence in the pathophysiology of ulceration is presented. Surgical and non-surgical treatment of the condition including surgical treatment of superficial and deep venous incompetence, compression therapy, and drug therapy is explored.Presented at the 37th Annual World Congress, International College of Angiology, Helsinki, Finland, July 1995.     

Endoscopic sclerotherapy in the treatment of gastric varices

Of 309 patients with portal hypertension, gastric varices were found in 48 (16 per cent). While the majority (88 per cent) of the patients had gastric varices in association with oesophageal varices, 6 (12 per cent) patients had 'isolated' gastric varices. Gastric varices were seen significantly (P less than 0.01) more often with grade 4 than with grade 3 varices. In 11 (28 per cent) of the 40 patients who completed sclerotherapy for oesophageal varices, gastric varices disappeared concurrently on eradication of oesophageal varices or during the following 6 months. Of the initial five patients with gastric varices who received direct intravariceal injections, four rebled; this technique was therefore replaced by combination (paravariceal + intravariceal) gastric variceal sclerotherapy. Emergency combination sclerotherapy successfully controlled bleeding from gastric varices in six of the eight treated patients. Thirty-two patients entered a programme of elective combination gastric variceal sclerotherapy. Variceal obliteration was achieved in 12 cases (38 per cent) and reduction in size was noted in another 7 patients (22 per cent) after a minimum of four courses. There were 11 (23 per cent) deaths, 8 due to uncontrolled bleeding from gastric varices and 3 due to hepatic coma. The other complications of gastric variceal sclerotherapy were minor and included retrosternal pain, fever and dysphagia. It is concluded that gastric varices often coexist with large oesophageal varices. If they persist for 6 months after eradication of oesophageal varices, a combination of paravariceal and intravariceal sclerotherapy should be attempted for their obliteration.     

Association of TNF-beta polymorphism with disease severity among patients infected with hepatitis C virus

The pathogenesis of chronic hepatitis C virus (HCV) infection remains unclear. Tumour necrosis factor alpha (TNF-alpha) is alleged to contribute in the pathogenesis of chronic HCV infection. Single nucleotide polymorphism in TNF-alpha and -beta genes could influence the outcome of HCV infection. The aim was to study single nucleotide polymorphism in TNF-alpha promoter region and Nco I polymorphisms in the TNF-beta gene in patients with chronic hepatitis C. Fifty-two patients with histologically proven chronic hepatitis, who had raised ALT levels (>1.5 x ULN) and were HCV RNA positive, were studied. Genotyping of -308 promoter variant of TNF-alpha was performed by PCR with primers that incorporated an Nco I restriction site. For PCR typing of the TNF-beta Nco I restriction fragment length polymorphism, sequence specific primers were used. Polymorphism in the TNF-alpha G/G, G/A and A/A allele was not different between HCV patients and healthy controls. TNF-beta A/A allele was significantly more common (P = 0.02) in patients (28.8%) as compared to controls (12.8%), whereas no significant difference was observed for TNF-beta G/A and G/G alleles [corrected]. Nco I TNF-beta A/A was strongly associated with -308 TNF-alpha G/G (RR of HCV persistence = 4.9), indicating possible linkage between TNF-beta A/A and TNF-alpha G/G allele. Patients with severe hepatic fibrosis more frequently had the TNF-beta A/A allele as compared to patients with mild disease (P = 0.04). Immunogenetic factors, such as single nucleotide polymorphisms in TNF-beta (A/A allele), may affect the natural course of HCV infection, in particular, the disease progression. Larger studies including cytokine expression profiles are needed to fully understand the contribution of the polymorphisms described in the pathogenesis of chronic hepatitis C.     

Malignant nasal paraganglioma: a case report and review of the literature

A rare case of malignant nasal paraganglioma is described. A 30 year old female patient presented with a one year history of bilateralnasal obstruction, nasal deformity and recurrent epistaxis. CT scan demonstrated an enhancing mass occupying both nasal cavities, right maxillary antrum and anterior ethmoid sinus. Histopathologic diagnosis was malignant paraganglioma. A total maxillectomy with excision of growth was performed. Post-operative radiotherapy and chemotherapy was given but patient expired before the completion of therapy. Nose being a rare site for paragangliomas, these lesions present a diagnostic challenge to histopathologists and clinicians alike. A review of the four previously described malignant nasal paragangliomas is also presented.     

Human immunodeficiency virus infection of the developing human nervous system

Human immunodeficiency virus (HIV), the etiologic agent of acquired immune deficiency syndrome (AIDS) and AIDS-related complex, has recently been implicated as a factor in the development of AIDS-related neurologic dysfunction and may be responsible for an increasing number of neonatal immunologic and neurologic disorders. However, as yet there is no model system available to investigate the interaction of HIV with the developing human nervous system in vitro. To approximate the intracellular events associated with HIV infection of the human fetus nervous system we infected cells obtained by enzymatic dissociation of aborted human fetus dorsal root ganglia and their attached spinal roots and nerves. The expression of the HIV gag gene protein products (p17 and p24) was detected in a subpopulation of cells with a nonneuronal morphology, reaching a maximum within 3 days. Although 70% of the nonneuronal cells were p17- and p24-positive 3 days after infection, a majority of the cell population survived acute HIV infection, with the expression of p17 and p24 decreasing below the limit of detection by 12 days postinfection. This system may prove useful for examining the neuropathology and neurobiology of acute, persistent, or latent HIV infection of the developing human nervous system.     

Constitutional genomic instability, chromosome aberrations in tumor cells and retinoblastoma

Although retinoblastoma (Rb) is initiated as a result of biallelic inactivation of the RB1 gene, additional genetic events (M3) in tumor cells are indicative of their role in the full transformation of retinal cells. We investigated the constitutional genetic instability by fragile site (FS) expression studies and checked its relationship with loci of tumor cytogenetics in a series of 36 retinoblastoma patients (34 nonfamilial and 2 familial cases). Tumor cytogenetics revealed -13/+13, del/t(13)(q14) (50%), +1/del/t(1p/q) (65%), +6/i(6p) (60%), and del(16)(q13)/(q22 approximately q23) (60%). Conventional cytogenetics in leukocytes revealed constitutional del(13q14) in five unilateral Rb (URB) and one trilateral Rb (TRB). Constitutional del(16)(q22) and t(6;12) were also identified in two cases. Constitutional FS analysis showed a significant increase in the cellular fragility, with high prevalence at 13q14, 3p14, 6p23, 16q22 approximately q23, and 13q22 loci in retinoblastoma patients (P<0.05). Patients with constitutional del(13)(q14) demonstrated higher fragility than those with normal constitution. A strong correlation between loci of constitutional FSs and loci of recurrent chromosomal abnormalities in tumors strengthen and support the proposal that FS loci present as inherent genomic instability in retinoblastoma. The chromosomal changes and resultant genetic mutations, along with RB1 mutation events, probably contribute synergistically to the development and progression of Rb malignancy. Implementation of fluorescence in situ hybridization to nonfamilial Rb on a large scale (113 cases) could detect constitutional RB1 deletion in 12.3% of cases, with equally higher incidence in URB (14.7%) and bilateral Rb (13.6%), demonstrating that the true prevalence of patients with predisposition to RB1 mutation in sporadic URB is definitely higher in our populations. Also, higher incidence of constitutional RB1 deletion mosaicism in unilateral than in bilateral Rb indicates that the constitutional genetic mosaicism in URB should be given serious consideration during genetic counseling.