Predictive characteristics of patients achieving glycaemic control with insulin after sulfonylurea failure.

AIM: We investigated the clinical and metabolic parameters in type 2 diabetic patients who were inadequately controlled on sulfonylurea (SU) before initiating insulin therapy to characterise patients who are likely to achieve target glycaemic control with insulin analogues. METHODS: A total of 120 Korean patients aged ≥ 40 years with insulin-naïve, poorly controlled, SU-treated type 2 diabetes were randomised on the basis of SU dose, and obesity with 1 : 1 ratio of insulin detemir (long-acting analogue; LAA) and 70% insulin aspart protamine and 30% insulin aspart (biphasic insulin analogue; BIA). Patients who failed to reach ≤ 20% glycated albumin (GA) at 3 weeks were switched to therapy with a twice-daily BIA for 16 weeks. RESULTS: Mean HbA(1c) , GA, fasting and stimulated plasma glucose levels were significantly reduced after 16 weeks compared with the baseline in all groups, and 40% of patients reached the target HbA(1c) ( ≤ 7%). Compared with responders, non-responders had significantly longer duration of diabetes and higher dose of glimepiride. However, there was no significant difference in insulin secretory profiles between responders and non-responders. Clinical factors such as diabetes duration, SU dose and BMI were independently associated with inadequate response to insulin analogues in patients with secondary failure. CONCLUSIONS: In type 2 diabetics with secondary SU failure, clinical parameters such as duration of diabetes (< 10 years), SU dose ( ≤ 4 mg) and BMI should be taken into consideration as important factors than laboratory indices related to ß-cell function when predicting the response to insulin analogues.

Circumferential osteotomy of the medial acetabular wall in total hip replacement for the late sequelae of childhood septic arthritis of the hip.

We performed 52 total hip replacements in 52 patients using a cementless acetabular component combined with a circumferential osteotomy of the medial acetabular wall for the late sequelae of childhood septic arthritis of the hip. The mean age of the patients at operation was 44.5 years (22 to 66) and the mean follow-up was 7.8 years (5 to 11.8). The mean improvement in the Harris Hip Score was 29.6 points (19 to 51) at final follow-up. The mean cover of the acetabular component was 98.5% (87.8% to 100%). The medial acetabular wall was preserved with a mean thickness of 8.3 mm (1.7 to 17.4) and the mean length of abductor lever arm increased from 43.4 mm (19.1 to 62) to 54.2 mm (36.5 to 68.6). One acetabular component was revised for loosening and osteolysis 4.5 years postoperatively, and one had radiolucent lines in all acetabular zones at final review. Kaplan-Meier survival was 94.2% (95% confidence interval 85.8% to 100%) at 7.3 years, with revision or radiological loosening as an end-point when two hips were at risk. A cementless acetabular component combined with circumferential medial acetabular wall osteotomy provides favourable results for acetabular reconstruction in patients who present with late sequelae of childhood septic hip arthritis.

Perineal rectosigmoidectomy for rectal prolapse: role of levatorplasty.

BACKGROUND: The management of full thickness rectal prolapse remains controversial. Although abdominal approaches have a lower recurrence rate than do perineal operations, they are associated with a higher morbidity. The aim of this study was to compare the outcomes of perineal rectosigmoidectomy with and without levatorplasty. METHODS: Between 1989 and 1999, a total of 109 consecutive patients (10 men) underwent 120 perineal procedures. These patients were retrospectively evaluated in two groups on the basis of the type of surgery received: perineal rectosigmoidectomy (PRS) or perineal rectosigmoidectomy with levatorplasty (PRSL). Subsequent functional outcome and physiological parameters were assessed. RESULTS: The patients had a mean age of 75.7 years (range, 23.0-94.8 years) and they were followed for an overall mean (in both groups combined) of 28.0 months (range, 0.4-126.4 months) after surgery. Mean duration of surgery was 78.1 min (SD=25.9) and 97.6 min (SD=32.3) in PRS and PRSL, respectively ( p=0.002, unpaired t test). There was no significant difference between the two groups in terms of hospital stay, morbidity or mortality. Recurrence rates and mean time interval to recurrence were, respectively, 20.6% and 45.5 months in PRS compared to 7.7% and 13.3 months in PRSL ( p=0.049, chi-square test; p=0.001, unpaired t test). Both groups had significant improvements in postoperative incontinence score ( p<0.0001, Wilcoxon's matched-pairs signed-ranks test), however, there were no significant changes in anorectal manometric findings and pudendal nerve terminal motor latency assessment. CONCLUSIONS: Perineal rectosigmoidectomy with levatorplasty is associated with a lower recurrence rate and a longer time to recurrence than perineal rectosigmoidectomy alone. Levatorplasty should be offered to patients when a perineal approach for rectal prolapse is selected.

Loss of heterozygosity and HIV infection in patients with anal squamous-cell carcinoma.

PURPOSE: This study was designed to determine whether loss of heterozygosity and/or microsatellite instability correlate with HIV infection and tumor recurrence after chemoradiation therapy in patients with squamous-cell carcinoma of the anus. BACKGROUND: The molecular mechanisms leading to the progression of HIV-related squamous-cell carcinoma of the anus are poorly understood. In particular, genetic alterations responsible for resistance to chemoradiation have important clinical and functional implications. METHODS: In a case-control study, we analyzed normal and tumor DNA samples of four patients with squamous-cell carcinoma of the anus who were successfully treated with chemoradiotherapy and four patients with radio-resistant squamous-cell carcinoma of the anus who required abdominoperineal resection for local recurrence. To determine the presence of microsatellite instability, we used the reference panel of five pairs of microsatellite primers recommended for colorectal cancer specimens. These include the microsatellite markers BAT25, BAT26, D5S346 (APC), D2S123 (hMSH2), and D17S250 (P53). In addition, we used microsatellite markers for loss of heterozygosity analyses that were tightly linked to tumor suppressor genes. These included D3S1611 (hMLH1), D17S513 (P53), D18S46 and 18qTA (DCC/SMAD4), D5S107 (APC), and CA5 (hMSH2). RESULTS: There were two HIV-positive and two HIV-negative patients in each group. Three HIV-positive patients (one in the chemoradiotherapy group and two in the nonchemoradiotherapy group) demonstrated loss of heterozygosity. In the chemoradiotherapy group, one HIV-positive patient demonstrated loss of heterozygosity at the hMLH1 locus. In the nonchemoradiotherapy group, two HIV-positive patients exhibited a total of four instances of loss of heterozygosity. One tumor had loss of heterozygosity at hMSH2 and DCC/SMAD4; another tumor demonstrated loss of heterozygosity at hMSH2 and APC. Microsatellite instability-low was found in two HIV-positive patients. No instances of loss of heterozygosity and microsatellite instability were detected in HIV-negative patients. CONCLUSION: Loss of heterozygosity and microsatellite instability, which reflect inactivation of tumor-suppressor genes and genomic instability, occur with increased frequency in HIV-associated squamous-cell carcinoma. These data demonstrate for the first time evidence of loss of heterozygosity at the APC and DCC/SMAD4 gene loci in anal carcinoma. Although the findings presented here need to be expanded in a larger study, the recurrent loss of heterozygosity at D2S123, which was demonstrated in HIV-positive patients with radio-resistant squamous-cell carcinoma of the anus, is notable.

Identification of phosphorylated form of cAMP/calcium response element binding protein expression in the brain stem nuclei at early stage of vestibular compensation in rats.

The present study was aimed at evaluating the time-dependent expressions of phosphorylated forms in the cAMP/calcium response element binding protein (pCREB) known to be one of transcription factors for immediate early genes in the brain stem nuclei of Sprague-Dalwey rats. Animals received surgical ablation of right peripheral vestibular labyrinth through a ventral approach. Immunohistochemical staining and digital image analysis systems were used to observe pCREB expressions in neuronal cells of the brain stem nuclei. The number of pCREB labeling neurons were increased with time, and peaked in the vestibular nuclear complex (VNC) bilaterally 1 h after unilateral labyrinthectomy (UL). In addition, high levels of phosphorylated CREB-like immunoreactivity (pCREB-LI) were also observed in bilateral cerebellum, olivary nuclear complex, and medullary nuclei. There was a rapid reduction of pCREB-LI in contralateral VNC but a slow reduction in the ipsilateral side 2 h after UL, causing an asymmetric number of pCREB labeling neurons between bilateral VNC (P<0.05). Thereafter pCREB-LI in bilateral VNC decreased to a very low level and returned to basal level 24 h after UL. These results suggest that the activation of the cAMP/calcium response element binding protein plays a role in the initial events of vestibular compensation in rats.

Laparoscopic procedures during the third trimester of pregnancy.

Pregnancy no longer is considered to be an absolute contraindication for laparoscopic procedures. Furthermore, clinically helpful guidelines are in place for laparoscopic procedures during pregnancy. However, laparoscopic operations in women in the third trimester have not yet been reported fully. We successfully operated on torsion of an ovarian cyst in a woman during her third trimester using laparascopic procedure. The patient experienced an uneventful recovery.

Effect of MK801 on cFos-like protein expression in the medial vestibular nucleus at early stage of vestibular compensation in uvulonodullectomized rats.

The purpose of this study was to evaluate the effect of uvulonodullectomy (UNL) on the expression of cFos-like protein (FLP) in the medial vestibular nucleus (MVe) during vestibular compensation and effect of MK801, an N-methyl-D-aspartate (NMDA) antagonist, on FLP expression in the brain stem nuclei at 6 h after unilateral labyrinthectomy (ULX) with UNL in Sprague-Dawley rats. Immunohistochemical staining was performed to visualize FLP in the brain stem nuclei and FLP-positive cells were counted by image analyzer. Lesion-induced asymmetric expression of FLP in the bilateral MVe was observed and maintained up to for 72 h in the ULX group, and 120 h in the UNL + ULX group. Moreover, spatial pattern of FLP expression in the bilateral MVe exhibited the marked difference between the ULX and UNL + ULX groups. MK801 treatment 6 h after ULX showed significant increase in the number of FLP in contralateral MVe (cMVe) of the ULX group, but decrease in cMVe of the UNL + ULX group. These results suggest that the lesion of vestibulocerebellum delays the temporal recovery of FLP expression in MVe and the vestibulocerebellar NMDA receptors relate to FLP expression in MVe.

Role of vestibulocerebellar N-methyl-D-aspartate receptors for behavioral recovery following unilateral labyrinthectomy in rats.

The purpose of current study was to elucidate whether vestibulocerebellar N-methyl-D-aspartate (NMDA) receptors are implicated in MK801 induced vestibular decompensation. Sprague-Dawley rats were unilaterally labyrinthectomized (ULX) and some of them were uvulonodullectomized before ULX (UNL + ULX). Number of spontaneous nystagmus (SN) and degree of head deviation (HD) were used as a parameter of behavioral recovery. MK801 treatment 6 h after ULX produced significant increases in SN and decreased HD in ULX rats, indicating decompensation. In marked contrast, however, MK801 treatment resulted in a great reduction of SN and HD in UNL + ULX rats; suggesting involvement of vestibulocerebellar NMDA receptors in MK801 induced decompensation during early stage of vestibular compensation.

Effect of sensory deprivation or electrical stimulation on acute vestibular symptoms following unilateral labyrinthectomy in rabbit.

The effect of sensory deprivation or electrical stimulation on vestibular compensation was investigated for 7 days after unilateral labyrinthectomy (ULX) in 50 rabbits. Eye movements induced by sinusoidal rotation of the whole body and spontaneous nystagmus were measured for vestibulo-ocular compensation, and head deviation was measured for vestibulospinal compensation. The rabbits were divided into 4 groups: one with ULX only (LX only), ULX with bilateral tarsorrhaphy (LX+TX), ULX with cervical dorsal root ganglionectomy (LX+GX), and a group stimulated electrically on the lesion-sided vestibular system with square pulse for 8 h/day (LX+ES). In LX only, the frequency of spontaneous nystagmus was 2.93 +/- 0.19 beats/sec just after ULX, declining to zero in 4 days. In eye movements induced by sinusoidal rotation on the 7th day after ULX, directional preponderance was 24-43% and gain decreased to 32-48% by rotation toward the intact side and 17-29% by rotation toward the lesion side, compared with that before ULX. Roll head tilt and yaw head tilt were 82 +/- 9 degrees, 45 +/- 6 degrees, respectively, on the 7th day. Recovery of vestibulo-ocular reflex and head deviation was delayed in LX+TX and LX+GX compared with that in ULX only, but recovery was enhanced in LX+ES. Therefore, in this study, electrical stimulation of the lesion side seemed to have a favorable effect on suppression of acute vestibular symptoms induced by unilateral vestibular lesion.