Influence of age on iminodipropionitrile-induced vestibular and neurobehavioral toxicities in rats

A direct association between aging and drug-induced dyskinesia has been reported by several investigators. Iminiodipropionitrile (IDPN), a prototype nitrile compound produces a motor syndrome in rodents, which resembles neuroleptic drug induced dyskinesia. In this investigation attempt has been made to study the effect of age on IDPN induced vestibular hair cell degeneration and resulting dyskinetic syndrome. Male Wistar rats aged 3, 6 and 12 weeks received IDPN in the doses of 0, 200 and 400 mg/kg, intraperitoneally for 3 consecutive days. IDPN-induced dyskinesia was assessed using a behavioral testing battery on days 3, 4, 5, 6, 7, 14, 21 and 28. The rats were sacrificed on day 28; temporal bones were excised for vestibular histopathology and sera were collected for measuring the indices of oxidative stress (glutathione and conjugated dienes). IDPN in the dose of 200 mg/kg produced dyskinesia in 12 weeks old rats, but failed to do so in 3 and 6 weeks old rats. The high dose of IDPN (400 mg/kg) caused dyskinesia in all age groups, however, its onset and severity were age-dependent. Older rats showed an early onset and significantly high incidence of dyskinesia as compared to younger rats. The susceptibility of rats to IDPN-induced behavioral deficits was proportional to oxidative stress and degeneration of sensory hair cells in the crista ampullaris.     

Blue spotted bladder--a manifestation of bladder amyloidosis. A case report

Bladder amyloidosis may represent a life-threatening condition, but may also be associated with milder clinical symptoms. Herein, we report two older males with a different type of apparently mild bladder amyloidosis, presenting as the "blue spotted bladder".     

ASO Visual Abstract: Will It Play in Peoria? A Pilot Study of a Robotic Skills Curriculum for Surgical Oncology Fellows

Annals of Surgical Oncology -     

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.     

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.