Positive and negative symptoms covary during clozapine treatment in schizophrenia

Although negative symptoms were traditionally considered to be unresponsive to neuroleptic medication, recent studies have demonstrated that negative symptoms do improve during neuroleptic treatment and that such improvement tends to occur concurrently with improvement in positive symptoms. Clozapine is an atypical neuroleptic that is effective in a significant proportion of otherwise neuroleptic-nonresponsive schizophrenic patients; in contrast to conventional neuroleptics, clozapine is also purported to possess unique efficacy in the amelioration of negative symptoms. How clozapine-associated reduction in negative symptoms relates to change in positive symptoms is not clear. To study the relationship between change in positive and negative symptoms during clozapine treatment, we monitored symptomatology in 40 DSM-III-R schizophrenic patients before and about 8 weeks after a trial of clozapine. Both positive and negative symptoms improved significantly. There was a significant correlation (r = .63,p <.01) between change in positive symptoms and change in negative symptoms; as with conventional neuroleptics, negative symptoms improved concomitantly with positive symptoms during clozapine treatment. Clozapine's apparent greater efficacy on negative symptoms may be related to its greater efficacy on positive symptoms in otherwise neuroleptic-refractory patients and its lesser propensity to cause extrapyramidal side-effects.     

Radical radiotherapy for T4 carcinoma of the skin of the head and neck: A multivariate analysis

Sixty-seven patients with 68 stage T4 carcinomas of the skin of the head and neck were treated with radical radiotherapy at the University of Florida between October 1964 and November 1989. Thirty-three lesions were previously untreated and 35 were recurrent. Twenty-nine lesions were squamous cell carcinomas, 37 were basal cell carcinomas, and 2 were basosquamous carcinomas. Minimum follow-up was 2 years. The 5-year local control, local control including surgical salvage, and cause-specific survival probabilities were 53%, 74%, and 75%, respectively. Local control rates with radiotherapy alone were poorer in patients with recurrent lesions (41% vs. 67%, p = .07) or bone involvement (40% vs. 62%, p = .08). Results were analyzed by multivariate methods using local control, local control with surgical salvage, and cause-specific survival as endpoints. The parameters analyzed were histology; size of primary lesion; previous treatment (previously untreated vs. recurrent); involvement of bone, nerve, or cartilage; and skeletal muscle invasion. Three important prognostic factors were identified, each predictive of poorer ultimate local control and cause-specific survival rates: (a) bone involvement (p < .01); (b) recurrent lesions (p < .01); and (c) nerve involvement (p < .02). Radiotherapy alone can control advanced carcinomas of the skin of the head and neck, although lesions that have recurred after prior treatment and those with involvement of bone or nerve are associated with a lower likelihood of cure.     

Representation of spatial frequency and orientation in the visual cortex

Knowledge of the response of the primary visual cortex to the various spatial frequencies and orientations in the visual scene should help us understand the principles by which the brain recognizes patterns. Current information about the cortical layout of spatial frequency response is still incomplete because of difficulties in recording and interpreting adequate data. Here, we report results from a study of the cat primary visual cortex in which we employed a new image-analysis method that allows improved separation of signal from noise and that we used to examine the neurooptical response of the primary visual cortex to drifting sine gratings over a range of orientations and spatial frequencies. We found that (i) the optical responses to all orientations and spatial frequencies were well approximated by weighted sums of only two pairs of basis pictures, one pair for orientation and a different pair for spatial frequency; (ii) the weightings of the two pictures in each pair were approximately in quadrature (1/4 cycle apart); and (iii) our spatial frequency data revealed a cortical map that continuously assigns different optimal spatial frequency responses to different cortical locations over the entire spatial frequency range.     

Regulation of the acid-labile subunit of the insulin-like growth factor ternary complex in patients with insulin-dependent diabetes mellitus and severe burns

OBJECTIVE Little information is available regarding the regulation of serum acid-labile subunit (ALS) in human disease. We have studied alterations in serum ALS of the insulin-like growth factor (IGF) ternary complex in children with untreated insulin-dependent diabetes mellitus (IDDM) and subjects with severe burns before and after insulin therapy. In addition, we have investigated the effect of insulin plus GH on serum ALS in burn patients. DESIGN Serum samples were obtained from children with newly diagnosed and untreated IDDM before the initiation of insulin therapy and 1 month thereafter. Serum samples were also obtained from adult patients with severe burns who were on a continuous infusion of a carbohydrate-rich enteral diet via nasogastric and duodenal catheters under basal conditions, after a 1-week period of continuous insulin infusion, and after an additional week of insulin plus recombinant GH. PATIENTS Twenty children and adolescents with untreated IDDM, aged 1.2–16 years, and 6 young adult patients with severe burns aged 17–28 years were studied longitudinally. Control sera were obtained from age, sex and pubertal status matched subjects (for children with IDDM) and from fed healthy adults. MEASUREMENTS Serum insulin, GH, cortisol and IGF-I were measured by radioimmunoassay, and serum ALS levels were assessed by Western immunoblot before and after treatment periods. RESULTS Serum ALS levels were lower in untreated children with IDDM (69 ± 6% of control children). Insulin therapy significantly increased serum ALS (79 ± 5%, P<0.05) in these children. Patients with severe burns also had lower serum ALS levels (79 ± 10% of control adults). After one week of insulin therapy serum ALS levels increased to 90 ± 15% of control values (P<0.05). Addition of GH to insulin therapy for another week did not significantly further increase serum ALS levels (95 ± 27%). Serum IGF-I concentrations increased nearly 2.5-fold in diabetic subjects and fourfold in burn subjects at the end of the study periods. There were no proteolytic fragments of ALS in the sera studied. The deglycosylation pattern of ALS did not differ between diabetic and control sera. CONCLUSION Serum ALS levels were diminished in children with untreated IDDM and were partially restored after the initiation of insulin therapy. Serum ALS levels were also diminished in patients with severe burn injury and restored by insulin treatment. Addition of GH to insulin therapy did not significantly increase serum ALS levels over levels obtained during insulin therapy alone. These decreases in serum ALS were smaller than the decrease in serum IGF-I concentrations in both conditions, suggesting that IGF-I is the limiting factor for the ternary complex formation in the catabolic states. Insulin may regulate circulating ALS levels in catabolic states and helps to restore the IGF system.     

Laparoscopic bowel surgery registry

Laparoscopic surgery has evolved rapidly since 1989. The American Society of Colon and Rectal Surgeons, the Society of American Gastrointestinal Endoscopic Surgeons, and the American College of Surgeons Commission on Cancer jointly sponsored a registry to identify as early as possible the patterns of practice and acute complications of laparoscopic colectomy. METHODS: Cases were voluntarily registered by community and academic surgeons. Information was entered in the EPI-5 database. RESULTS: One thousand fifty-six cases were contributed by 118 surgeons; 763 patients were completed laparoscopically. The most common indication for surgery was cancer in 453 patients. The right colon (n=364) and sigmoid (n=294) were most frequently resected. Respondents felt adequate cancer resections were performed. Although several unique complications were noted, intraoperative complications were similar in type and frequency to open cases. CONCLUSION: Laparoscopic colorectal surgery can be performed with acceptable complications. It remains unclear if this approach is adequate for long-term management of colon and rectal cancer.Read at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

Effects of Myocardial Water Exchange on T1 Enhancement during Bolus Administration of MR Contrast Agents

Interpretation of first-pass myocardial perfusion studies employing bolus administration of T₁ magnetic resonance (MR) contrast agents requires an understanding of the relationship between contrast concentration and image pixel intensity. The potential effects of myocardial water exchange rates among the intravascular, interstitial, and cellular compartments on this relationship are controversial. We directly studied these issues in isolated, nonbeating canine interventricular septa. Myocardial T₁ was measured three times/s during bolus transit of intravascular (albumin-Gd-DTPA and poly-lysine-Gd-DTPA) and extracellular (gadoteridol) contrast agents. For polylsine-Gd-DTPA, the peak changes in myocardial 1/T₁ (ΔR1) scaled nonlinearly with perfusate contrast concentration whereas a linear relationship would be expected for fast water exchange among the vascular, interstitial, and cellular compartments. For all agents, the peak ΔR1 were much smaller than the values expected on the basis of fast myocardial water exchange. The data demonstrate that in isolated myocardial tissue, myocardial T₁ enhancement during bolus administration of contrast can be strongly affected by myocardial water exchange for both intravascular and extracellular MR contrast agents.     

The Physiology of Gastrocystoplasty: Once a Stomach, Always a Stomach

To determine the physiology of acid secretion after gastrocystoplasty with the body of the stomach we performed a prospective standardized 3-day study in 13 children (median age 12.5 years) who had undergone bladder augmentation/replacement (median postoperative period 2 years). Urinary pH and titratable acid, and serum gastrin levels were measured after gastric distention with a meal and bladder distention with urethral filling at baseline and after medication with a histamine-2 receptor antagonist or an anticholinergic agent. Five children underwent cystoscopy and biopsy of the gastric and native segments of the gastrocystoplasty.

In the fasting state pH was neutral, there was no titratable acid in the urine and serum gastrin level was normal in all cases. After a meal urinary acid secretion and serum gastrin level increased markedly. After each medication half of the patients demonstrated marked inhibition of urinary acid secretion after a meal while response was partial in the remainder. In none of the patients was there significant alteration in the pattern of gastrin secretion. Bladder distention did not result in urinary acid secretion or gastrin secretion. The cystoscopic and histological appearance of the native bladder and stomach segment of the gastrocystoplasty in the 5 patients was normal. We conclude that the gastric body segment used in gastrocystoplasty continues to secrete acid as though it were part of the stomach. The secretion of acid in the urine can be decreased with histamine-2 receptor antagonist or anticholinergic medication.