Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons

1. The effects of the volatile anesthetics enflurane, halothane, and isoflurane on gamma-aminobutyric acid (GABA) receptor-mediated inhibitory postsynaptic currents (IPSCs) were studied in cultured rat hippocampal neurons. The experimental concentrations of anesthetics were measured directly using gas chromatography. All three anesthetics increased the overall duration of IPSCs, measured as the time to half-decay (T1/2). Clinically effective concentrations of anesthetics [between 0.5 and 1.5 times MAC (minimum alveolar concentration)] produced between 100 and 400% increases in T1/2. These effects were fully reversible, and did not involve alterations in the reversal potential for the IPSC (EIPSC). 2. The decay of the IPSC was fitted as a sum of two exponential functions, yielding a fast component (tau fast = 20 ms), and a slow component (tau slow = 77 ms), such that the fast component accounted for 79% of the IPSC amplitude and 52% of the total charge transfer. All three anesthetics produced concentration-related increases in the amplitude and charge transfer of the slow component, while simultaneously decreasing the amplitude and charge transfer of the fast component. Thus T1/2 approximated tau fast under control conditions, but approximated tau slow in the presence of the anesthetics. 3. Varying the calcium chelating agents in the recording pipettes had no effect on the quality or magnitude of alterations in IPSC kinetics produced by halothane, suggesting that variations in intracellular calcium levels are not required for the effect of halothane on the time course of the IPSC. 4. The (+)-stereoisomer of isoflurane produced greater increases in the duration of the IPSC than the (-)-isomer when applied at approximately equal concentrations, suggesting that there is a structurally selective site of interaction for isoflurane that modulates the GABAA receptor. 5. These results suggest that the previously shown abilities of volatile anesthetics to potentiate responses to exogenously applied GABA and to prolong the duration of GABA-mediated synaptic inhibition may be due to an alteration in the gating kinetics of the GABAA receptor/channel complex. Prolongation of synaptic inhibition in the CNS is consistent with the physiological effects that accompany anesthesia and may contribute to the mechanism of anesthetic action.     

Human papillomavirus-specific serologic response in vulvar neoplasia

We describe a case of positional dyspnea due to compression of the tracheobronchial tree by an extensive thoracic aneurysm. In a 77-year-old woman with long-standing systemic hypertension, intermittent anterior chest pain gradually developed over several years. She had no history of asthma or thoracic trauma. She was admitted to our hospital because of sudden, severe shortness of breath. The breathlessness was markedly worse when she lay on her back or on her right side. On physical examination, she was in acute respiratory distress with cyanosis, severe hypertension (180/110 mmHg), tachycardia, and inspiratory stridor. A chest X-ray film showed loss of volume and nearly complete radiopacity of the left hemithorax. Arterial blood gas analysis revealed an arterial oxygen partial pressure of 54.8 mmHg, a carbon dioxide partial pressure of 39.8 mmHg, and an oxygen saturation of 84.5 percent on room air. Computed tomographic examination of the thorax showed dilation of the aortic arch and descending aorta, and marked compression of the trachea and the left main bronchus. Examination with a fiberoptic bronchoscope revealed extrinsic compression of the trachea just proximal to the carina. The patient's symptoms stabilized. However, she did not undergo surgery because of her age and because of the size of the aneurysm. She died due to rupture of the aneurysm.     

Human papillomavirus investigation of patients with cervical intraepithelial neoplasia 3, some of whom progressed to invasive cancer

Unstable expansion of the CTG repeats in the 3' untranslated region encoding a member of the protein kinase family in the q13.3 band on chromosome 19 is a mutation specific for myotonic dystrophy. To examine the correlation between clinical expression and CTG trinucleotide repeat length, we carried out Southern blot analysis in a family with myotonic dystrophy. In this pedigree, the expanded CTG repeats were transmitted maternally. The mother had three female children. The mother had about 200 CTG repeats, and the number of repeats for each child was about 800, 1500 and 1600 in birth order. The mother and the patient with 800 repeats were unaware of muscle weakness or myotonia. Symptoms were present from age 3 years in the patient with 1500 repeats and from birth in the one with 1600 repeats. Although the mother menstruated regularly, the patients with 800 and 1500 repeats both menstruated irregularly, and the one with 1600 repeats has never menstruated. The age of onset and severity of the disease were correlated with the size of the expanded repeats. Endocrinological studies revealed that the basal levels of the gonadotropins, PRL and E2 were within normal range, and a pituitary response to LHRH was observed. These data suggest that the amenorrhea and menstrual irregularities were caused by a suprahypophyseal dysfunction. When expanded CTG repeats are transmitted maternally, abnormal products resulting from the metabolic disturbance in the affected mother may harm the fetus in utero. A heterozygous fetus, who has more CTG repeats, may be unable to metabolize the pathologic products sufficiently and therefore may become more severely affected. This may explain the exclusive maternal transmission of congenital myotonic dystrophy.     

Glomerular and tubular function in glycogen storage disease

Urinary protein and calcium excretion were assessed in 77 patients with the hepatic glycogen storage diseases (GSD): 30 with GSD-I (median age 12.4 years, range 3.2-32.9 years), 25 with GSD-III (median age 10.5 years, range 4.2-31.3 years) and 22 with GSD-IX (median age 11.8 years, range 1.2-35.4 years). Inulin (Cinulin) and para-aminohippuric acid (CPAH) clearances were also measured in 33 of these patients. Those with GSD-I had significantly greater albumin (F = 15.07, P < 0.001), retinol-binding protein (RBP) (F = 14.66, P < 0.001), N-acetyl-beta-D-glucosaminidase (NAG) (F = 9.41, P < 0.001) and calcium (F = 7.41, P = 0.001) excretion than those with GSD-III and GSD-IX. GSD-I patients (n = 18) also had significantly higher Cinulin (F = 5.57, P = 0.009), but CPAH did not differ (F = 0.77, NS). Renal function was normal in GSD-III and GSD-IX patients. In GSD-I, Cinulin (r = -0.51, P = 0.03) and NAG excretion (r = -0.40, P = 0.03) were inversely correlated with age, whereas albumin excretion was positively correlated with age (r = +0.41, P = 0.03). RBP and calcium excretion were generally high throughout all age groups. Hyperfiltration in GSD-I is associated with renal tubular proteinuria that occurs before the onset of significant albuminuria. Deficiency of glucose-6-phosphatase within the proximal renal tubule may primarily cause tubular dysfunction, glomerular hyperfiltration being a secondary phenomenon.     

Caudascopic experiences and a new patho-anatomic concept for treatment of sciatica

Osteotomy has been used in treatment of unstable intertrochanteric hip fractures in an attempt to increase the stability of the fracture fragments. We have assessed this stability in a randomised prospective study on 138 patients, all having been fixed by dynamic hip screen, comparing anatomical reduction with medialisation osteotomy. The groups were similar in terms of age, gender and fracture configuration. There was no difference in final results in both groups except that operation time was longer in osteotomy group and the blood loss was more. We found no clear benefit from osteotomy and therefore recommend anatomical reduction and fixation by a sliding hip screw in most cases. Rarely, a fracture configuration which does not allow anatomical reduction may benefit from an osteotomy.