The Workup for Bariatric Surgery Does Not Require a Routine Upper Gastrointestinal Series

Background: Morbid obesity is a serious disease that afflicts over five million Americans, threatening their health with such co-morbidities as diabetes, arthritis, pulmonary failure and stroke. Surgery is the only effective therapy, providing long-term control of weight, diabetes, pulmonary failure, and hypertension for as long as 14 years. Because the operation presents a major expense, this study examined whether X-ray examination of the gut could be omitted safely as a cost-saving measure. Methods: The records of 814 consecutive morbidly obese patients who underwent gastric bypass were reviewed to determine: (1) whether these individuals had undergone an upper gastro-intestinal (GI) series, and (2) if these studies influenced therapy or caused cancellation or postponement of surgery. Results: Of the 814 patients, 657 (80.7%) underwent a preoperative GI radiography. Of these examinations, 393 (59.8%) were normal, with the following abnormalities in the remaining 264: hiatal hernia, 164; esophageal reflux, 39; Schatzki's ring, 18; small bowel diverticula, four; renal stones, four; malrotation, three; gall stones, two; pyloric ulcer, one; possible pelvic mass, one; calcified leiomyoma, one; and dysphagial lusoria, one. None of these findings resulted in cancellation or a delay in surgery. Conclusions: The upper GI series can be safely omitted from the routine preoperative evaluation of patients undergoing gastric bypass. At a cost of $741.00 per examination, this change represents significant potential savings. Similar evaluations of other routine preoperative tests may well provide a better basis for the evaluation of these complex patients.     

Accommodative hysteresis under static and dynamic stimulus conditions

The influence of continuous variation in dioptric demand on the accommodative hysteresis induced at near distances was examined in 14 visually-normal young adults. Tonic accommodation was measured before and after 10 minutes of sustained focus using a constant stimulus at 5 D, 6.5 D, and 8 D, as well as a stimulus which slowly and alternately increased and decreased over the continuous range from 5 D to 8 D. For approximately half the subjects, dioptric demand had to be very high (8 D) under static conditions to produce moderate but significant hysteresis, yet little or no attenuation of the effect occurred under the dynamic condition. For other subjects who consistently showed very large tonic changes (1.4 D or more) under static conditions, the hysteresis effect generated under dynamic conditions was greatly reduced (approximately 50 per cent) in magnitude. These findings suggest that the degree to which continuous variation in dioptric demand will disrupt the adaptive process may depend on individual differences in the rate and/or maximum level of tonic accommodative change. Such a relationship could have bearing on the particular strategy recommended for individuals who tend to experience blur at distance following nearwork.     

Human ovarian-carcinoma cell lines and companion xenografts: a disease-oriented approach to new platinum anticancer drug discovery

Summary A disease-oriented approach to the discovery of novel platinum anticancer drugs has been established through the setting up of parallel human ovarian-carcinoma cell lines and xenografts. The correlation between in vitro and in vivo antitumour activity was determined for four reference platinum agents (cisplatin, carboplatin, iproplatin and tetraplatin) in eight companion lines. Two methods of assessing antitumour effect were used in vitro (tritiated thymidine incorporation and sulforhodamine B staining) and three were applied in vivo [28-day treated/control (T/C) ratio, growth delay and specific growth delay]. In vitro, large differences in cytotoxicity across the cell lines were observed for each drug. This was also reflected in the xenografts for cisplatin and carboplatin and, to a lesser extent, for iproplatin. A correlation analysis of in vitro vs in vivo data revealed a high, statistically significant positive correlation for cisplatin and a strong positive correlation for carboplatin. However, for the two platinum(IV) drugs, the correlation was less good. In particular, tetraplatin was markedly less active in vivo (showing a general lack of activity against all of the tumour lines) than its in vitro potency against the cell lines predieted, resulting in poor correlation coefficients. These human tumour panels may be valuable for the elucidation of both cellular/molecular and corresponding in vivo pharmacological mechanisms of platinum drug resistance. Moreover, the HX/62 and SKOV-3 tumour lines, which exhibit a level of intrinsic resistance to the four reference agents both in vitro and in vivo (and which were derived from patients who had not received prior platinum therapy), represent particularly useful evaluation models for the discovery of novel broad-spectrum platinum drugs.This study was supported by grants to the Institute of Cancer Research from the Cancer Research Campaign and the Medical Research Council, the Johnson Matthey Technology Centre and Bristol Myers Squibb Oncology     

Thalamocortical projections activated by phrenic nerve afferents in the cat

This study identified thalamocortical projections activated by respiratory afferents. Cortical evoked potentials were recorded in the right primary somatosensory cortex of the cat following electrical stimulation of the left C5 root of the phrenic nerve. The majority of primary sites were located in the vicinity of the postcruciate dimple, in area 3a near the 3a/3b border, corresponding to the trunk region of the cortical body map. Retrograde fluorescent tracers injected at the sites of primary activation produced labeled cells in the oralis nucleus of the ventroposterior complex [4]. Control injections made in adjacent cortical areas not activated by phrenic stimulation resulted in labeling in the ventroposterior complex which did not overlap that seen with injections of primary activation sites. We conclude that respiratory muscle afferents in the phrenic nerve elicit activity in the trunk region of primary somatosensory cortex via specific thalamocortical projections originating in the oralis portion of the thalamic ventroposterior complex.     

Novel therapeutic approaches for multiple myeloma

Summary: Multiple myeloma (MM) affects 15 000 new patients annually in the US, with 50 000 total patients, and remains incurable. Our preliminary in vitro and animal studies suggest a role for MM–host interactions in regulating MM cell growth, drug resistance, and migration in the bone marrow. Importantly, treatment strategies which target mechanisms whereby MM cells grow and survive in the bone marrow, including thalidomide and its potent immunomodulatory derivatives and proteasome inhibitor PS‐341, can overcome classical drug resistance in preclinical and early clinical studies.     

Polycystic ovary syndrome and the single nucleotide polymorphisms of methylenetetrahydrofolate reductase: a pilot observational study

Polycystic ovary syndrome (PCOS), insulin resistance and overall mortality due to diabetes and coronary artery disease are higher in South Asians than in Caucasians. Aims: We compared the prevalence of the C677T and A1298C single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene in South Asian and Caucasian women, its association with folate and homocysteine (Hcy) metabolism, and its relevance to future atherogenic events. Methods and results: 71 women were recruited for the study: South Asian PCOS (21) plus controls (9) and Caucasian PCOS (25) plus controls (16). Anthropometric and laboratory parameters were compared. South Asian PCOS women were significantly hyperandrogenic and exhibited a greater degree of insulin resistance. Caucasian PCOS women had higher plasma Hcy concentrations with a 1.9 times higher frequency of the T allele than the South Asian PCOS group. In the presence of this variant allele, plasma Hcy levels appear to be higher in both PCOS groups. The South Asians had a 1.8 times higher frequency of the C allele than the Caucasians; however, the overall frequency was comparable in the two PCOS groups. The frequency of homozygosity, i.e. TT677 and CC1298, was 7.2% and 4.9% in the Caucasians and 0% and 16.6% in the South Asian recruits, respectively. Dietary inadequacies in the South Asian women can influence their plasma folate and B12 concentrations resulting in hyperhomocysteinemia which, in combination with dyslipidaemia and insulin resistance, can lead to long-term atherogenic consequences. CONCLUSIONS: Current data suggests that the mechanisms of atherothrombosis have separate pathways in the two ethnic groups. Larger studies exploring the current theme need to be carried out in the PCOS groups to obtain adequate insight.     

Repair of severed peripheral nerves: Comparison of the “de Medinaceli” and standard microsuture methods

The return of function following transection of the rat sciatic nerve has been assessed after repair by either standard microsurgical techniques (i.e., the use of microsutures to coapt the severed ends) or the new repair technique introduced by de Medinaceli and coworkers. The regeneration after transection was compared with that following sciatic nerve crush, i.e., a lesion in which the return of function is near optimal. Return of function was monitored serially using walking track analysis (i.e., the sciatic functional index, which indicates overall functional performance), the ability to spread the toes (which indicates intrinsic function in the foot), and the determination of muscle twitch tension of the middle digit. Function in the nerve crush group returned to within the normal range by 53 days, but function in the transection and repair groups did not return to normal before the rats were perfused at 85 postoperative days. However, the function regained when nerves were repaired with the de Medinaceli technique was significantly superior to that regained after repair with microsutures. Histological examination of the repair site (at 85 days) revealed that the regenerated nerve fibers in the de Medinaceli group crossed the site of anastomosis in a relatively orderly fashion, whereas they were more randomly arranged when microsutures were used. However, there was no statistical difference between the two groups in the number of regenerated fibers present in the distal stump. The increase in function in the de Medinaceli group may therefore arise primarily from an increase in the proportion of regenerating fibers which reach appropriate targets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of peptide T in patients with Acquired Immunodeficiency Syndrome (AIDS)

1. The pharmacokinetics of Dalal-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiecy disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intraveneous (i.v.) or intranasal (i.n.), via metered sprayer, administration.

2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearence rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA.

3. Bioavailabilty, determined for a 2 mg test dose in six individuals was 9.3 ± 6.9 nmol/L. Peak plasma levels of 41 ± 30 nmol/L after 10 mg i.n., 2.8 ± 5.9 nmol/L after 2mg i.n., and 0.13 ± 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months.