Human leukocyte interferon-α in cream,for the treatment of genital warts in asian women a placebo-controlled,double-blind study

The purpose of this double-blind, placebo-controlled study was to determine and compare the clinical efficacy and tolerance of human leukocyte -interferon (incorporated 2 × 10⁶ IU/g) in hydrophilic cream to cure genital warts. Preselected Asian female patients (n=150) aged 18–40 years (mean 22.5), with the clinical and biopsy-confirmed diagnosis of genital warts (mean 2.64), predominantly flat vaginal condylomas, were randomly allocated to 3 parallel groups. Each patient was given a coded tube containing 80 g placebo/active preparation with a graduated applicator. Patients were instructed to inject 6 g of the either alloted placebo/active cream deep into the vagina thrice a day for 3 consecutive days (group A) or 4 consecutive days (group B) per week, and if not cured the same treatment was extended to 3 more weeks (maximum 4 weeks active treatment). To assess the clinical efficacy patients were examined on a week-to-week basis. A total clearance of warts (biopsy-confirmed) was evaluated as a complete cure. Patients cured during the treatment were spared further treatment and were requested to visit us after 16 weeks for relapse control. As for the remaining patients, empty tubes were collected, and similarly coded replacement tubes were given for further treatment (in total 588 tubes were used). By the end of the treatment 57.2% lesions (227/397) were eliminated in all the groups: 48% patients in group A, 90% patients in group B, and 10% patients in placebo groups taken as completely cured. Of the 150 patients 128 (85.3%) did not complain of any drug-related adverse symptoms. Transitory increase in body temperature (mean 38.4°C), accompanied by headache (14.6%) and generalized itching (6.6%) were the most frequently reported side effects; however, treatment was well tolerated by all the patients, and there were no dropouts. Our findings indicate that clinical efficacy is dose dependent, that is, the results of group B were significantly superior to that of group A (P < 0.05). Of the 49.3% cured patients (74/150) followed up for 6 months (monthly basis) seven had a relapse, and none had reinfection. It is concluded that clinical efficacy of leukocyte interferon-a to cure genital warts is dose dependent. These results further support the view that leukocyte interferon-a incorporated in hydrophilic cream can be considered a reliable, safe, and home-based treatment to cure vulvar and vaginal warts.Abbreviation HPV human papillomavirus     

Brain stem auditory evoked potentials in medical coma

BAEPS are coming up as an important investigatory tool in the hands of present clinicians and have a diagnostic and prognostic significance. The present study was carried on 25 patients. BAEPS were recorded at the time of admission and analysed. Absent BAEPS were associated with high mortality. Abnormal BAEPS were seen in infective and CVA group. Followup BAEPS showed no change in those patients who died.     

Echigo-1: a panencephalopathic strain of Creutzfeldt-Jakob disease: ultrastructural studies of the optic nerve

The Echigo-1 strain of CJD was isolated by Mori and colleagues (1989) from a case of 33-year-old female with a panencephalopathic type of CJD. An incubation period following intracerebral inoculation of hamsters with 10% cleared suspension of the Echigo-1-affected brain was approximately six months. We report here ultrastructural changes which are comparable with those in the white matter of another panencephalopathic type of CJD, the Fujisaki strain of CJD (GSS) passaged in mice. Vacuoles developed within myelinated axons: within axoplasm or within the myelin sheath and these were accompanied by exuberant reaction of macrophages and hypertrophic astrocytes. Axons underwent Wallerian degeneration and dystrophic neurites were also seen. Most important, we observed proliferation of inner mesaxons. Cross-sectional profiles of innumerable myelinated fibers contained membranous organelles which were continuous with the inner lamellae of the oligodendroglial cells. These unusual proliferations of inner mesaxon formed whorls and elaborated loops. In some axons, proliferation was so severe that loops of mesaxon filled the whole cross-section of the axon. Occasionally, we observed intrusion of the membranous tongue of the inner mesaxon into axoplasm. This study presents a second panencephalopathic model of CJD available in small laboratory rodents. It is important because this is the only such model in hamsters and it may be used for comparative studies of different strains of agent in the same host; thus far only mouse and hamster model have been available for comparative studies.     

Metabotropic glutamate receptor subtypes independently modulate neuronal intracellular calcium

Metabotropic glutamate receptors (mGluRs) modulate several G-protein-related signal transduction pathways including intracellular calcium (iCa(2+)) that control both neuronal development and demise. As an initial investigation, we characterized the ability of specific mGluR subtypes to modulate iCa(2+) by using Fura-2 microfluorometry in primary hippocampal neurons. Activation rather than inhibition of the metabotropic system with the group I and group II mGluR agonist 1S, 3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), the specific group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG), and the specific group II agonist (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (LCCG-I) increased iCa(2+) with increasing concentrations. In contrast, the group III mGluR agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4) produced no significant increase in iCa(2+). Through the pharmacological modulation of individual mGluR subtypes, we further examined the role of iCa(2+) release by the mGluR system. Release of iCa(2+) by both 1S,3R-ACPD and LCCG-I was prevented only through the administration of the antagonists (2S)-alpha-ethylglutamic acid (EGlu; mGluR2 and mGluR3) and (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-IV; mGluR2), suggesting that the mGluR2 subtype was responsible for the release of iCa(2+). As a control, the group I antagonists, L(+)-2-amino-3-phosphonopropionic acid (L-AP3) and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), prevented DHPG release of iCa(2+) but were ineffective against iCa(2+) release by 1S,3R-ACPD. Although extracellular calcium influx did not significantly contribute to the release of iCa(2+) by the mGluR system, pharmacological inhibition of calcium-induced calcium-release-sensitive calcium pools played a critical role in the release of iCa(2+). Further characterization of the cellular calcium pools modulated by the mGluR subtypes may provide greater insight into the mechanisms that mediate neuronal function.     

The surgical treatment of carcinoma of the colon and rectum: an index of quality care and sociologic and geographic distribution.

A comparative experience of 474 patients with primary carcinoma of the colon and rectum has been evaluated in several hospital settings, with particular respect to patient populations, geographic distribution, and surgical characteristics. The differences and similarities are interpreted with caution but may provide a format by which significant objective determinants become the basis for subsequent assessment of quality care in an illness which is prevalent and amenable to relatively standardized operative management. No difference in quality of medical care provided was detectable across the sociologic and geographic boundaries studied. Notable increases in extent of neoplasm and severity of co-existent illness in the urban, "indigent" population adversely influenced both short and long-term mortality rates.     

Controlled trial of frusemide as an antiepileptic drug in focal epilepsy

1 The antiepileptic activity of oral frusemide (120 mg daily) was compared with that of an identical placebo in a double-blind crossover trial in fourteen patients with severe focal epilepsy who were receiving long-term therapy with established antiepileptic drugs.

2 A statistically significant reduction in the frequency of focal fits was seen with the active drug.

3 Marked drowsiness occurred in three patients during frusemide therapy, causing their withdrawal from the trial.

4 A slight, but significant, rise in serum phenobarbitone concentrations was observed during frusemide therapy, but no change was seen in serum primidone or phenytoin concentrations.

5 Frusemide significantly lowered plasma sodium and potassium concentrations, and increased plasma bicarbonate.

     

Electrogustometry: strengths,weaknesses, and clinical evidence of stimulus boundaries

Electrogustometry is well established as a clinical tool for the estimation of taste detection thresholds. Nevertheless, the user is sometimes unaware of the impact of superficially minor procedural and psychophysical factors upon the reliability and comparability of threshold estimates. The inherent strengths and limitations of the procedure are outlined, and aspects of the control and specification of the stimulus that moderate threshold measures are discussed. In addition, threshold estimates from two individuals with severe unilateral taste loss are used to illustrate the level at which anodal dc current may elicit common, rather than taste, sensation. Where chorda tympani section is complete and historical (older than 7–14 days), very high stimulus levels, conservatively over 5 µA/mm² (100 µA linear current with a 5‐mm diameter electrode), are required to activate trigeminal responses.     

Abdominal cerebrospinal fluid pseudocyst

A case of an abdominal cerebrospinal fluid (CSF) pseudocyst in a patient with a ventriculoperitoneal shunt is reported to illustrate this known but rare complication. In the setting of a VP shunt, the frequency of abdominal CSF pseudocyst formation is approximately 3.2%, often being precipitated by a recent inflammatory or infective process or recent surgery. Larger pseudocysts tend to be sterile, whereas smaller pseudocysts are more often infected. Ultrasound and CT each have characteristic findings.     

Acute rejection-associated tubular basement membrane defects and chronic allograft nephropathy

BACKGROUND: Acute rejection is a major risk factor for chronic allograft nephropathy, although the link(s) between these events is not understood. The hypothesis of this study is that alterations in tubular basement membranes (TBMs) that occur during acute rejection may be irreversible and thereby play a role in the development of chronic allograft nephropathy. METHODS: Fourteen renal transplant patients were selected, each having had two or more biopsies performed (42 total). All biopsies were scored for acute and chronic rejection using Banff 1997 criteria. The initial biopsy showed only acute interstitial rejection (type I rejection). No biopsies contained significant chronic arterial lesions of chronic vascular rejection. The entire cortex was examined on Jones methenamine silver-stained sections at x400 for interruption in TBM staining. The number of tubules with TBM abnormalities was counted, and the renal cortical area was measured by image analysis. Periodic acid-Schiff/immunoperoxidase stain was performed on 12 acute rejection biopsies stained for laminin, cytokeratin 7, CD3, CD20, and CD68. Controls consisted of 11 biopsies (8 negative for rejection and 3 acute tubular necrosis). RESULTS: Numerous TBM alterations in silver staining were identified as being associated with acute rejection and tubulitis, consisting of abrupt TBM discontinuities and/or extreme attenuation with segmental or complete absence of TBM. A loss of TBM matrix proteins was confirmed by absent laminin staining in areas of acute rejection and tubulitis. There was herniation of tubular cells into the interstitium through TBM defects confirmed by cytokeratin staining. The TBM defects were spatially associated with inflammatory cells, particularly macrophages. When the biopsies were divided into two groups, <10 and> 10 TBM breaks/mm2, there were statistically significant morphologic and clinical correlations. The number of TBM disruptions correlated with the serum creatinine at the time of biopsy, a combined Banff t + i score, the difference in tubular atrophy between the initial and most recent biopsy and the difference between the nadir creatinine and most recent creatinine. CONCLUSION: Damage to TBM develops in acute rejection as a consequence of interstitial inflammation and tubulitis. These lytic events correlate with the later development of clinical and morphologic evidence of chronic injury in the absence of arterial injury of chronic rejection. We suggest that chronic allograft nephropathy may have an inflammatory interstitial origin.     

Cell-mediated immune response is better preserved by laparoscopy than laparotomy

BACKGROUND: This study compares the effects of carbon dioxide pneumoperitoneum versus laparotomy on cellular-mediated immune response in a murine model. METHODS: Sixty-eight female C3H/He mice were sensitized to keyhole limpet hemocyanin (KLH) and to a mouse mammary carcinoma cell line (MC2) before surgery. Animals were randomized into 4 groups: group I, anesthesia (control); group II, pneumoperitoneum with carbon dioxide; group III, extraperitoneal wound; group IV, laparotomy. All animals were challenged subsequently with KLH and MC2 tumor cells. Delayed-type hypersensitivity skin reaction (DTH) to KLH was measured on postoperative days (PODs) 1, 2, 4, and 5. Tumor growth was assessed weekly as an indicator of postoperative cellular immune response. RESULTS: Compared with preoperative values, postoperative DTH skin reactions were significantly less for all PODs in groups III and IV (P < .05), on POD 1 and 4 in group II (P < .05) and POD 4 for group I (P < .05). Group IV showed significantly fewer DTH skin reactions for all PODs compared with groups I and II (P < .05) and all PODs except on day 2 compared with group III (P < .05). Tumor growth was significantly increased at postoperative week 2 (n = 3/17 mice) and 3 (n = 4/17 mice) in group IV, when compared with groups I and II (P < .05). CONCLUSIONS: Cellular immunity is preserved after carbon dioxide pneumoperitoneum compared with extraperitoneal incisions and laparotomy as measured by DTH and the ability to reject an immunogenictumor.